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PMID: 23329412 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.

Bioinformatics (Oxford, England) ·Vol. 29 ·No. 4 ·2013-02-15 ·Pages 499-503

Levine TP, Daniels RD, Gatta AT, Wong LH, Hayes MJ

Abstract

Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known. Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).

MeSH Terms
Amyotrophic Lateral Sclerosis/genetics C9orf72 Protein Frontotemporal Dementia/genetics Guanine Nucleotide Exchange Factors/chemistry,classification Humans Protein Structure, Tertiary Proteins/chemistry,classification,genetics Sequence Homology, Amino Acid
Chemicals
C9orf72 Protein C9orf72 protein, human Guanine Nucleotide Exchange Factors Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Levine Timothy P
Department of Cell Biology, UCL Institute of Ophthalmology, Bath St, London EC1V 9EL, UK. tim.levine@ucl.ac.uk
Daniels Rachel D
Gatta Alberto T
Wong Louise H
Hayes Matthew J
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Article Info
Journal
Bioinformatics (Oxford, England)
Abbr.
Bioinformatics
ISSN
1367-4811
DOI
10.1093/bioinformatics/bts725
Email
tim.levine@ucl.ac.uk
Published
2013-02-15
Epub
2013-00-16
Pages
499-503
Language
English
Region
England
NLM ID
9808944
PMCID
PMC3570213
Subset
IM
Grants
Wellcome Trust · 093445/B/10/Z · United Kingdom
Medical Research Council · J006580 · United Kingdom
External Links
PubMed source DOI: 10.1093/bioinformatics/bts725 PMC Full Text View journal details
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