Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of deletion constructs of the 5' flanking region of rat c-mos gene was positioned upstream to the CAT gene and transfected into muscle and non-muscle cells. CAT activities revealed that a region located downstream of a TATA box and containing the proximal transcription start site is the muscle c-mos promoter. This promoter is more efficient in L6 alpha 1 myoblasts than in L6 alpha 1 myotubes but not in C3H10T1/2 cells. Gel shift assays demonstrated that nuclear proteins from myoblasts and myotubes formed complexes migrating differently. Footprinting analyses showed that nuclear proteins from L6 alpha 1 myoblasts protected a DNA fragment located at position nt -979 to nt -938 relative to the first ATG of the rat c-mos ORF while nuclear proteins from myotubes protected the DNA between nt -998 to nt -928. Furthermore one of protein - DNA complexes containing the proximal transcription start site, included a consensus sequence TGTC(AGT/TCG)CC(A/T)G present in the initiator element (Inr) of several genes. Southwestern blot analysis pointed to a 82kDa polypeptide as a potential candidate for trans acting factor in myoblasts. In L6 alpha 1 myotubes this polypeptide is replaced by other proteins of 40-42kDa and 82kDa. An interplay between these two complexes may constitute a developmental as well as a physiologically regulated mechanism that modulates c-mos expression during the early stages of myogenesis.
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PMID:Identification of a cis acting element responsible for muscle specific expression of the c-mos protooncogene. 844 78

The molecular basis of the variable species-specific peroxisomal and/or mitochondrial targeting of the enzyme alanine-glyoxylate aminotransferase 1 (AGT) has been studied in human fibroblasts by confocal immunofluorescence microscopy after intranuclear microinjection of various human, rabbit, marmoset, and feline AGT cDNA constructs. The expression of full-length human and rabbit AGT cDNA led to an exclusively peroxisomal distribution of AGT. However, the distribution of feline and marmoset AGT depended on the cDNA construct injected. In both species, injection of the short cDNAs (from transcripts that occur naturally in marmoset liver but not in feline liver) led to an exclusively peroxisomal distribution. However, injection of the long cDNAs (from transcripts that occur naturally in both species) led to most of the AGT being targeted to the mitochondria and only a small, yet significant, fraction to the peroxisomes. Reintroduction of the 'ancestral' first potential translation initiation site into human AGT cDNA led to an 'ancestral' distribution of AGT (i.e. both mitochondrial and peroxisomal). Deletion of the second potential translation start site from the long feline cDNA led to a distribution that was almost entirely mitochondrial, which suggests that most peroxisomal AGT encoded by the long cDNA results from internal translation initiation from this site with the consequent loss of the N-terminal mitochondrial targeting sequence. Expression of rabbit cDNA and the short marmoset and feline cDNAs in cells selectively deficient in the import of peroxisomal matrix proteins showed that peroxisomal AGT in all these species is imported via the peroxisomal targeting sequence type 1 (PTS1) import pathway. The almost complete functional dominance of the N-terminal mitochondrial targeting sequence over the C-terminal PTS. which was not due to any direct interference of the former with peroxisomal import, was maintained even when the unusual PTS1 of AGT (KKL in human) was replaced by the prototypical PTS1 SKL. The results demonstrate that the major determinant of alanine-glyoxylate aminotransferase subcellular distribution in mammals is the presence or absence of the mitochondrial targeting sequence rather than the peroxisomal targeting sequence. Various strategies have arisen during the evolution of mammals to enable the exclusion of the mitochondrial targeting sequence from the newly synthesised polypeptide, all of which involve the use of alternative transcription and/or translation initiation sites.
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PMID:Molecular basis of the variable mitochondrial and peroxisomal localisation of alanine-glyoxylate aminotransferase. 891 33

The nucleotide sequences of the inv, yadA, and ail adhesin-invasin genes were analyzed in 24 strains of the main and nonmain Yersinia pestis subspecies, which were isolated from natural plague foci in Russia and neighbor countries, and ten Y. pseudotuberculosis strains. All of the five plague agent subspecies (main, caucasica, altaica, ulegeica, and hissarica) had the inv and yadA genes altered by insertion of the IS element and a single nucleotide deletion, respectively, as was earlier observed for the Y. pestis strains KIM and CO92. Consequently, the strains lacked functional activity of the Inv and YadA proteins. The ail gene of the main and ulegeica subspecies had a missense mutation, which replaced Val138 with Phe in the Ail protein. The strains of the caucasica subspecies had an AGT insertion in the ail gene, resulting in Ser148 insertion in the polypeptide chain. The changes in the ail sequence probably exerted no effect on ail expression, since the strains of all subspecies were resistant to blood serum complement.
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PMID:[Sequence analysis of the yadA, inv, and ail genes and their expression in the main and nonmain Yersinia pestis subspecies and Yersinia pseudotuberculosis]. 2073 63

Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5'-phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.
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PMID:Protein homeostasis defects of alanine-glyoxylate aminotransferase: new therapeutic strategies in primary hyperoxaluria type I. 2395 97