Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level

Authors

Carlos Romá-Mateo, Instituto de Biomedicina de Valencia, Spain
Daniel Moreno, Instituto de Biomedicina de Valencia, Spain
Santiago Vernia, Instituto de Biomedicina de Valencia, Spain
Teresa Rubio, Instituto de Biomedicina de Valencia, Spain
Travis M. Bridges, University of KentuckyFollow
Matthew S. Gentry, University of KentuckyFollow
Pascual Sanz, Instituto de Biomedicina de Valencia, Spain

Abstract

BACKGROUND: Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.

RESULTS: After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex.

CONCLUSIONS: We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.

Document Type

Article

Publication Date

7-28-2011

Notes/Citation Information

Published in BMC Evolutionary Biology, v. 11, 225.

© 2011 Romá-Mateo et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1186/1471-2148-11-225

Repository Citation

Romá-Mateo, Carlos; Moreno, Daniel; Vernia, Santiago; Rubio, Teresa; Bridges, Travis M.; Gentry, Matthew S.; and Sanz, Pascual, "Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level" (2011). Molecular and Cellular Biochemistry Faculty Publications. 26.
https://uknowledge.uky.edu/biochem_facpub/26