Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial hypobetalipoproteinemia, a syndrome associated with low plasma cholesterol levels, can be caused by apoB gene mutations. We identified a healthy 42-year-old man whose total plasma cholesterol level was 80 mg/dl. His plasma very low density lipoprotein (VLDL) contained a unique truncated apoB species, apoB-83, in addition to the normal B apolipoproteins, apoB-100 and apoB-48. Virtually no apoB-83 was detectable in his low density lipoprotein (LDL). From the subject's kindred, we identified nine other hypocholesterolemic subjects whose VLDL contained apoB-83. A tendency for cholelithiasis was noted in the apoB-83 heterozygotes, particularly in the older individuals. From the apparent size of apoB-83 on SDS-polyacrylamide gels and its reactivity with apoB-specific monoclonal antibodies, we estimated that it would contain approximately 3700-3800 amino acids. DNA sequencing of apoB genomic clones from two affected individuals revealed that apoB-83 was caused by a C----A transversion in exon 26 of the apoB gene (apoB cDNA nucleotide 11458). This mutation converts Ser-3750 (TCA) into a premature stop codon (TAA) and creates a unique MseI restriction endonuclease site. Thus, a single nucleotide transversion in the apoB gene results in a unique truncated apoB species, apoB-83, and the clinical syndrome of familial hypobetalipoproteinemia.
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PMID:A truncated species of apolipoprotein B, B-83, associated with hypobetalipoproteinemia. 152 80

An apolipoprotein (apo) B-specific monoclonal antibody, MB19, detects a commonly occurring two-allele genetic polymorphism in human apoB (Young, S. G., S. J. Bertics, L. K. Curtiss, D. C. Casal, and J. L. Witztum. 1986. Proc. Natl. Acad. Sci. USA. 83: 1101-1105). Antibody MB19 binds to two different allotypes of apoB, MB19(1) and MB19(2), with high and low affinity, respectively. The epitope for antibody MB19 is located within apoB-100 thrombolytic fragment T4 (apoB-100 amino acid residues 1-1297). In this study, we examined the relationship of the MB19 polymorphism to a C----T nucleotide substitution at apoB cDNA nucleotide 421. This nucleotide substitution results in a Thr----Ile substitution at apoB-100 amino acid 71, and it changes an ApaLI restriction endonuclease site in the apoB gene. The nucleotide substitution was easily detectable by ApaLI digestion of a 141-base pair fragment of the apoB gene obtained by enzymatic amplification of genomic DNA. In 62 subjects, the MB19 phenotype, as determined by radioimmunoassays, correlated perfectly with the ApaLI restriction site polymorphism in the amplified DNA. The apoB allotype MB19(1) is associated with an Ile at residue 71 and the absence of the ApaLI site, whereas the apoB allotype MB19(2) is associated with a Thr at residue 71 and the presence of the ApaLI site. We conclude that the amino acid substitution at residue 71 probably accounts for the MB19 polymorphism in apoB.
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PMID:An ApaLI restriction site polymorphism is associated with the MB19 polymorphism in apolipoprotein B. 247 Aug 48

ApoB is a large glycoprotein with an apparent molecular mass of 550 kDa on NaDodSO4/PAGE. It is a major constituent of most lipoproteins and plays an important role in their metabolism. Recently, apoB cDNA clones have been isolated from an expression library made with mRNA from a human hepatoma cell line. These clones, which were all 1.5-1.6 kilobases (kb) long and corresponded to the 3' end of apoB mRNA, were used to demonstrate that hepatic apoB mRNA is approximately 22 kb long. In the current report, a probe derived from one of these cDNA clones, pB8, was used for in situ hybridization experiments to map the human gene for apoB, APOB, to the distal half of the short arm of chromosome 2. This probe was also used to analyze somatic cell hybrids and, in agreement with the in situ hybridization studies, concordancy was demonstrated with chromosome 2. In addition, two hybrids with chromosome 2 translocations that contain only the short arm reacted with the pB8 probe. A third hybrid with a complex rearrangement of chromosome 2, which deleted an interstitial region and the tip of the short arm of chromosome 2, did not react. These data indicate that APOB maps to either 2p21-p23 or 2p24-pter. In further studies, DNA from normal individuals, digested with the restriction endonuclease EcoRI and subjected to Southern blot analysis with the pB8 probe, revealed a two-allele restriction fragment length polymorphism (RFLP). The major allele was 11 kb, and the minor allele was 13 kb. The minor allele was present with a frequency of 20-25%. The inheritance of the two alleles was studied in an informative family, and they segregated in a typical autosomal Mendelian fashion. The mapping studies provide the means for understanding the relationship of the APOB locus to others in the human genome, whereas the demonstration of an APOB RFLP increases our ability to assess the role of this locus in determining plasma lipoprotein levels.
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PMID:Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism. 300 43

Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a minority of cases is due to a truncation producing mutation in the apoB gene. We have identified an apoB mutation in a 40-year old hypobetalipoproteinemic man with Type II diabetes mellitus. Immunoblotting of plasma revealed a major band for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55. The proband's 75-year old father with Type II diabetes and a non-diabetic daughter also possessed the truncated protein. Direct sequencing of the amplified fragment of genomic DNA revealed a C-->T transition at nt 7692 in exon 26 of the apoB gene. This substitution yielded a premature stop codon at residue 2495 and abolished a BsaI restriction endonuclease site. The identical mutation has been described previously; however, the genotypes and ancestors of the kindred were different, suggesting that the mutation may have occurred independently. The majority of apoB-55 was eluted as particles smaller than LDL-sized apoB-100, and floated mostly between the LDL and HDL density range. It is worth noting that despite the presence of Type II diabetes, both the proband and his father have very low plasma lipid levels and neither have any clinically manifest macrovascular complications.
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PMID:Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55). 954