cDNA cloning and characterization of an atrophin-1 (DRPLA disease gene)-related protein.
Dentatorubral and pallidoluylsian atrophy (DRPLA) is a progressive neurological disorder characterized by neuronal degeneration, especially in the cerebellar dentate nucleus. DRPLA is caused by an unstable expansion of a CAG trinucleotide repeat coding for glutamine in a gene of unknown function, termed atrophin-1, located on chromosome 12. To gain additional understanding of atrophin-1, we have isolated a second member of the atrophin-1 gene family by screening rat cDNA libraries. The 1006-amino-acid product of this gene, which we have termed rat atrophin related protein(rARP), does not contain a glutamine repeat, but it does contain two regions of alternating acidic and basic amino residues similar to those found in atrophin-1. rARP is widely expressed as both a 7.4- and a 9.4-kb message, with enrichment in cerebellum and testis. Like atrophin-1, the rARP in vitro translation product migrates more slowly on SDS-polyacrylamide gel electrophoresis than predicted by molecular weight. We conclude that, at least in the rat, polyglutamine is not an essential feature of the atrophin family of genes.
Khan
F A
FA
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Margolis
R L
RL
Loev
S L
SL
Sharp
A H
AH
Li
S H
SH
Ross
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics*; D005786:Gene Expression Regulation; D015723:Gene Library; D005796:Genes; D005973:Glutamine; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D018911:Trinucleotide Repeats
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; C095278:atrophin-1; D005973:Glutamine