Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProt release 2013_09

Published September 18, 2013


With a little help from my... Lassa virus

Dystroglycan provides a physical link between components of the extracellular matrix, including laminin, and the intracellular actin cytoskeleton. This link is crucial for a number of cellular processes, including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, cell migration and epithelial polarization.

The dystroglycan protein is extensively glycosylated at multiple sites, and an unusual O-linked glycan is required for proper interaction with extracellular matrix ligands including laminin. Glycosyltransferases responsible for this modification were first identified using classical biochemical techniques, and mutations in the associated genes were identified in patients presenting with one of a number of dystroglycanopathies. These are a heterogeneous group of disorders characterized by muscular dystrophy that can be associated with brain anomalies, mental retardation, eye malformations, and other clinical symptoms. However until recently some 50% of newly diagnosed cases of dystroglycanopathy showed no significant association with variants in known glycosyltransferase genes.

To address this issue, Jae et al., 2013 developed a powerful approach to dystroglycanopathy candidate gene identification that exploits another, less beneficial property of dystroglycan. The hemorrhagic Lassa virus binds to glycosylated dystroglycan during infection, the efficiency of which depends on the glycosylation level. By using gene-trap insertion mutagenesis the authors were able to identify genes whose inactivation conferred resistance to Lassa virus infection, which by extension may include regulators of the level of dystroglycan glycosylation. These genes included all those previously known to be associated with a dystroglycanopathy, as well as several novel candidates. Exon sequencing of a panel of patients with severe dystroglycanopathy identified variants in two of them, POMK/SGK196 and TMEM5, while confirming the absence of variants in known dystroglycanopathy genes. The other candidates await further characterization.

We may be about to witness the elucidation of the underlying genetic causes of a range of dystroglycanopathies, disorders associated with defective dystroglycan modification, through the use of a deadly virus that normally targets the affected protein.

As of this release, all proteins involved in dystroglycanopathies can be retrieved from UniProtKB/Swiss-Prot with the keyword Dystroglycanopathy.

UniProtKB news

Removal of the cross-reference to Pathway_Interaction_DB

Cross-references to Pathway_Interaction_DB have been removed.

Changes to the controlled vocabulary of human diseases

New diseases:

Modified diseases:

Deleted diseases:

  • Cataract, pulverulent, juvenile-onset, MAF-related
  • 2-aminoadipic 2-oxoadipic aciduria

Changes to keywords

New keywords:

Modified keywords:

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again