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
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
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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.