Analysis of the human VPS13 gene family☆
Section snippets
Identification and structure of human genes similar to CHAC
We performed a BLAST analysis of chorein variant A against DNA and protein databases, and a number of hypothetical proteins showed high similarity: KIAA1421, FLJ20136, and FLJ10381 on chromosome 15q21.3; FLJ20583 and KIAA0532 on 8q22; and FLJ10619 and KIAA0453 on 1p36. The different proteins encoded by potential genes in each chromosome region showed similarity with a different region of chorein. These results suggested that there were three genes similar to CHAC, one on each of the
Discussion
We report here the characterization of a human gene family homologous to yeast Vps13. Rampoldi et al. [1] and Ueno et al. [2] reported VPS13A (formerly CHAC) as the gene that is mutated in the neurodegenerative disorder ChAc. We have identified three new genes, VPS13B, VPS13C, and VPS13D, encoding proteins similar to chorein. VPS13B has recently been reported as COH1 [7], altered in the recessive disorder Cohen syndrome.
Identification and structure determination of VPS13 genes
Chorein was compared against the databases using BLAST facilities at EMBL-EBI http://www.ebi.ac.uk/blast2/) and NCBI http://www.ncbi.nlm.nih.gov/BLAST/). The detected human proteins were located on the genome using the MapViewer facility http://www.ncbi.nlm.nih.gov/mapview/) for Homo sapiens, build 31, and the mRNA sequences available aligning in the respective region were obtained following the Evidence Viewer link. Gaps in the cDNA sequence were transiently filled according to GenomeScan
Acknowledgements
This work was supported by the Wellcome Trust. A.V.-B. is supported by a Marie Curie postdoctoral fellowship. A.V. was supported by a predoctoral fellowship from the Italian Ministero dell'Universita' e della Ricerca Scientifica e Tecnologica. C.D.-S. was supported by a Wellcome Trust Prize Studentship. A.P.M. is a Wellcome Trust Principal Research Fellow.
References (37)
Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport
Am. J. Hum. Genet
(2003)Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways
J. Biol. Chem
(2001)- et al.
Evolution of alternative splicing: deletions, insertions and origin of functional parts of proteins from intron sequences
Trends Genet
(2003) - et al.
How prevalent is functional alternative splicing in the human genome?
Trends Genet
(2004) RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer
Trends Genet
(1999)- et al.
Alternative RNA splicing in the nervous system
Prog. Neurobiol
(2001) - et al.
Alternative splicing in the nervous system: an emerging source of diversity and regulation
Biol. Psychiatry
(2003) - et al.
Eukaryotic domain evolution inferred from genome comparisons
Curr. Opin. Genet. Dev
(2003) - et al.
The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway
Trends Biochem. Sci
(1996) Evolution by gene duplication: an update
Trends Ecol. Evol
(2003)
Genome and protein evolution in eukaryotes
Curr. Opin. Chem. Biol
T-Coffee: a novel method for fast and accurate multiple sequence alignment
J. Mol. Biol
Accurate formula for P-values of gapped local sequence and profile alignments
J. Mol. Biol
A conserved sorting-associated protein is mutant in chorea-acanthocytosis
Nat. Genet
The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis
Nat. Genet
Clinical features and molecular bases of neuroacanthocytosis
J. Mol. Med
Allele-specific suppression of a defective trans-Golgi network (TGN) localization signal in Kex2p identifies three genes involved in localization of TGN transmembrane proteins
Mol. Cell Biol
SOI1 encodes a novel, conserved protein that promotes TGN–endosomal cycling of Kex2p and other membrane proteins by modulating the function of two TGN localization signals
J. Cell Biol
Cited by (0)
- ☆
Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. AJ608769, AJ626859, AJ608772, AJ608773, AJ608770, AJ608771, AJ626860, AJ626861, AJ608774, and AJ608775.
- 1
These two authors contributed equally to this article.