Linked Life Data

1339350

Source:http://linkedlifedata.com/resource/pubmed/id/1339350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-8-25
pubmed:databankReference
pubmed:abstractText
In mammals, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) is species dependent, with the proportion of AGT targeted to mitochondria varying between 0% and greater than 90%, the remainder being located in the peroxisome. In order to extend our studies on the molecular evolution of intracellular targeting of AGT, we have investigated the organization and expression of the AGT genes of rabbit, which has all of its AGT located in the peroxisome, and marmoset, which has approximately 50% of its AGT located in the peroxisome and 50% in the mitochondrion. Southern-blot analysis indicates that, in both of these species, AGT is encoded by a single-copy gene, as has previously been shown for human (all AGT in the peroxisome) and rat (50% AGT in the peroxisome and 50% in the mitochondrion). Comparison of the cDNA sequences encoding marmoset, rabbit, human and rat AGT, combined with transcript mapping and in vitro mitochondrial protein-import analysis, has provided a molecular explanation for the differential targeting of AGT in these species. As in the rat, marmoset AGT is synthesized in two forms, via the use of alternative transcription and translation-initiation sites. These two forms of AGT differ only in the presence or absence of a 22-amino-acid amino-terminal peptide, which acts as a cleavable mitochondrial-targeting sequence, directing the longer form of AGT to mitochondria. The shorter form of AGT, lacking the mitochondrial-targeting sequence, is presumed to be localized in the peroxisomes. In humans and rabbits, similar but distinct evolutionary mutational events within the AGT gene have resulted in exclusion of the region encoding the mitochondrial-targeting sequence from the open reading frame, explaining the exclusive peroxisomal localization of AGT in these species. We discuss the impact of these results on our understanding of both the evolution of species dependence of AGT subcellular distribution and the recent identification of amino acid changes in human AGT which result in mistargeting of this protein to mitochondria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
207
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
757-66
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:1339350-Alanine Transaminase, pubmed-meshheading:1339350-Amino Acid Sequence, pubmed-meshheading:1339350-Animals, pubmed-meshheading:1339350-Base Sequence, pubmed-meshheading:1339350-Biological Evolution, pubmed-meshheading:1339350-Biological Transport, pubmed-meshheading:1339350-Blotting, Southern, pubmed-meshheading:1339350-Callithrix, pubmed-meshheading:1339350-Cell Compartmentation, pubmed-meshheading:1339350-Cloning, Molecular, pubmed-meshheading:1339350-DNA, pubmed-meshheading:1339350-Gene Expression, pubmed-meshheading:1339350-Genes, pubmed-meshheading:1339350-Humans, pubmed-meshheading:1339350-Microbodies, pubmed-meshheading:1339350-Mitochondria, pubmed-meshheading:1339350-Molecular Sequence Data, pubmed-meshheading:1339350-Oligodeoxyribonucleotides, pubmed-meshheading:1339350-RNA, Messenger, pubmed-meshheading:1339350-Rabbits, pubmed-meshheading:1339350-Rats, pubmed-meshheading:1339350-Sequence Alignment, pubmed-meshheading:1339350-Transaminases
pubmed:year
1992
pubmed:articleTitle
Molecular evolution of alanine/glyoxylate aminotransferase 1 intracellular targeting. Analysis of the marmoset and rabbit genes.
pubmed:affiliation
Biochemical Genetics Research Group, Clinical Research Centre, Harrow, England.
pubmed:publicationType
Journal Article, Comparative Study