Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine carbamoyl transferase (Oct) is an X-linked gene which exhibits tissue-specific expression. To determine whether methylation of specific CpG sequences plays a role in dosage compensation or tissue-specific expression of the gene, 13 potentially methylatable sites were identified over a 30-kilobase (kb) region spanning from approximately 15 kb upstream to beyond exon II. Fragments of the Mus hortulanus Oct gene were used as probes to establish the degree of methylation at each site. By considering the methylation status in liver (expressing tissue) versus kidney (nonexpressing tissue) from male and female mice, the active and inactive genes could be investigated on active and inactive X-chromosome backgrounds. One MspI site, 12 kb 5' of the Oct-coding region, was cleaved by HpaII in liver DNA from males but not in kidney DNA from males and thus exhibited complete correlation with tissue-specific expression of the gene. Six other sites showed partial methylation, reflecting incomplete correlation with tissue-specific expression.
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PMID:Differential methylation of the ornithine carbamoyl transferase gene on active and inactive mouse X chromosomes. 282 19

Ornithine-delta-aminotransferase (OAT) is a nuclear-encoded, mitochondrial matrix enzyme which, in rat, is expressed as basal levels in most tissues but is induced in liver by high dietary protein and in kidney by estrogen and thyroxine administration. In man, the hereditary deficiency of OAT results in ornithine accumulation and the blinding disease gyrate atrophy of the choroid and retina. We cloned near full length rat and human liver OAT cDNAs and demonstrated OAT expression in a variety of tissues from each species. We mapped the human OAT structural gene to chromosome 10, cloned 40 kilobase pairs of genomic DNA containing the complete OAT structural gene, and determined its organization. It is 21 kilobase pairs in length, and contains 11 exons. Exon 2 has been absent from all cDNAs studied and was detected by homology to X-linked processed OAT pseudogenes. The 5'-flanking region of the OAT gene has features of housekeeping genes (GC enrichment and three Sp1 binding consensus sequences) and tissue-specific, inducible genes (TATA box-like element and two CCAAT boxes). A 22-base pair region of partial dyad symmetry containing homology to estrogen responsive elements overlaps the OAT transcription site. Another 5' sequence, GTATCCTGCCCTC, is homologous to sequences in the promoter regions of the genes of three urea cycle enzymes.
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PMID:Human ornithine-delta-aminotransferase. cDNA cloning and analysis of the structural gene. 317 May 46

Ornithine Transcarbamylase Deficiency, an X-linked disorder, is the most common cause of inherited urea cycle disorders. Approx. 90 mutations that produce reduced levels of ornithine transcarbamylase (OTCase) activity have been identified in patients [Tuchman (1993) Hum. Mutat. 2, 174-178; Tuchman and Plante (1995) Hum. Mutat. 5, 293-295]. A model of the three-dimensional structure of OTCase, developed on the basis of its homology to the catalytic subunit of Escherichia coli aspartate transcarbamylase (ATCase) [Tuchman, Morizono, Reish, Yuan and Allewell (1995) J. Med. Genet. 32, 680-688], and in good agreement with the crystal structure of Pseudomonas aeruginosa OTCase [Villeret, Tricot, Stalon and Dideberg (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10762-10766], indicates that many mutations that produce severe clinical symptoms are at the active site or buried in the interior of the protein. However, one of the few recurrent mutations, R277W, an alteration that produces a milder phenotype of ornithine transcarbamylase deficiency, is located in the model in a loop remote from the active site that is analogous to a similar loop (the 240's loop, a flexible loop of the catalytic chain of Escherichia coli aspartate transcarbamylase, comprised of residues 230-250) of ATCase. Human wild-type OTCase and the R277W mutant have been cloned and overexpressed in E. coli and a rapid and efficient purification method utilizing the bisubstrate analogue, Ndelta-(phosphonacetyl)-L-ornithine, has been developed and used to purify both proteins. Gel chromatography indicates both are trimeric. The pH dependence of the kinetic parameters of the wild-type enzyme is similar to that of E. coli OTCase [Kuo, Herzberg and Lipscomb (1985) Biochemistry 24, 4754-4761], suggesting that its catalytic mechanism is similar, although its maximal activity is approx. 10-fold less. Compared with the wild-type, the R277W mutant has nearly 70-fold lower affinity for L-ornithine, shows no substrate inhibition, and its thermal stability is reduced by 5 degrees C. Its reduced affinity for L-ornithine, which in turn results in lower activity at physiological concentrations of ornithine, as well as its reduced stability, may contribute to the clinical effects that it produces.
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PMID:Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonaemia. 906 86