Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC-->GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC-->AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity.
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PMID:Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187. 779 54

Known types of pairings between mRNA bases and tRNA nucleosides are shown to be consistent with the notion of a translation space TS constructed such that certain wobble-pairings cannot be used in the same translation system without engendering confusion between keto-final codon twins like AAU(ASN)/AAG(LYS) and between amino-final codon twins like AAC(ASN)/AAA(LYS). When TS is abstractly formalized using Coxeter's face-first three-dimensional projection of a four-dimensional hypercube, the resulting model suggests a specific configurational logic for codon recognition by cognate tRNAs. Although this logic will in general permit codons and anticodons to form matching configurations whose loci are six lines parallel to the axis of a cylinder, confusion of keto-final and amino-final codon twins may result from wobble-pairings whose loci are the two of these lines off the surface of the cylinder.
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PMID:A geometric model for codon recognition logic. 805 66

An inherited fibrinogen variant, fibrinogen Bern I, was isolated from plasma of an asymptomatic woman. Routine coagulation studies showed prolonged thrombin and reptilase clotting times. Fibrinogen concentration was diminished when determined by a functional assay, but was normal by the heat precipitation method. The release of fibrinopeptides A and B was not delayed. Two-dimensional gel electrophoresis of mercaptolyzed fragments D of fibrinogen, obtained by digestion with plasmin, showed an abnormal electrophoretic mobility in the gamma-chain remnants of fragments D1 and D2 from fibrinogen Bern I, whereas conversion of D2 to D3 by plasmin resulted in the loss of the abnormal charge, suggesting that the structural abnormality in this variant is located in the region gamma 303 through 356. The molecular defect in fibrinogen Bern I was identified by sequence analysis of genomic DNA amplified by polymerase chain reaction and cloned in M13mp19. The triplet AAC coding for asparagine at position gamma 337 was found to be substituted by AAA coding for lysine. We conclude that the substitution gamma 337 Asn-->Lys in fibrinogen Bern I is responsible for defective polymerization of fibrin monomers and for impaired protection by calcium against plasmic degradation.
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PMID:Fibrinogen Bern I: substitution gamma 337 Asn-->Lys is responsible for defective fibrin monomer polymerization. 840 Feb 60

Six naturally occurring but rare alleles of sn-glycerol-3-phosphate dehydrogenase (Gpdh) in Drosophila melanogaster have been investigated in this study. They all belong to a class of GpdhUF (ultra-fast) alleles, because their electrophoretic mobilities are faster than that of the GpdhF (fast) allele. The GpdhUF variants are widespread, and have been reported from five continents. DNA sequence analysis has shown that the change in electrophoretic mobility was in each allele caused by a single amino acid residue substitution in the encoded protein. In the XiamenUF allele it is a substitution of lysine (AAA) to asparagine (AAT) in exon 1 (residue 3). An asparagine (AAT) to aspartate (GAT) change was found in exon 6 (residue 336) in the IowaUF and NetherlandsUF alleles. The mobility of the RaleighUF allele was altered by a valine (GTG) to glutamate (GAG) substitution in exon 3 (residue 76). Two mutations were detected in the BrazzavilleUF allele: a lysine (AAG) to methionine (ATG) substitution in exon 2 (residue 68) is responsible for the ultra-fast phenotype of this variant, while a tyrosine (TAT) to phenylalanine (TTT) substitution in exon 4 (residue 244) is not expected to alter the electrophoretic mobility of the encoded protein. These results indicate that the GpdhUF alleles originate from different mutational events, and only two of them--IowaUF and NetherlandsUF--might share a common ancestry. The GPDH activity of the IowaUF allele is intermediate between those of the GpdhS and GpdhF control stocks. The other GpdhUF variants have lower activities than the controls: XiamenUF--83%, RaleighUF--80% and BrazzavilleUF--73% of the GpdhF control.
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PMID:Molecular structure of rare but geographically widespread sn-glycerol-3-phosphate dehydrogenase 'ultra-fast' electrophoretic alleles in Drosophila melanogaster. 890 Nov 36

In the mitochondrial genome of the hemichordate Balanoglossus carnosus, the codon AAA, which is assigned to lysine in most metazoans but to asparagine in echinoderms, is absent. Furthermore, the lysine tRNA gene carries an anticodon substitution that renders its gene product unable to decode AAA codons, whereas the asparagine tRNA gene has not changed to encode a tRNA with the ability to recognize AAA codons. Thus, the hemichordate mitochondrial genome can be regarded as an intermediate in the process of reassignment of mitochondrial AAA codons, where most metazoans represent the ancestral situation and the echinoderms the derived situation. This lends support to the codon capture hypothesis. We also show that the reassignment of the AAA codon is associated with a reduction in the relative abundance of lysine residues in mitochondrial proteins.
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PMID:Codon reassignment and amino acid composition in hemichordate mitochondria. 952 Apr 30

It has been inferred from DNA sequence analyses that in echinoderm mitochondria not only the usual asparagine codons AAU and AAC, but also the usual lysine codon AAA, are translated as asparagine by a single mitochondrial (mt) tRNAAsn with the anticodon GUU. Nucleotide sequencing of starfish mt tRNAAsn revealed that the anticodon is GPsiU, U35 at the anticodon second position being modified to pseudouridine (Psi). In contrast, mt tRNALys, corresponding to another lysine codon, AAG, has the anticodon CUU. mt tRNAs possessing anti-codons closely related to that of tRNAAsn, but responsible for decoding only two codons each-tRNAHis, tRNAAsp and tRNATyr-were found to possess unmodified U35 in all cases, suggesting the importance of Psi35 for decoding the three codons. Therefore, the decoding capabilities of two synthetic Escherichia coli tRNAAla variants with the anticodon GPsiU or GUU were examined using an E.coli in vitro translation system. Both tRNAs could translate not only AAC and AAU with similar efficiency, but also AAA with an efficiency that was approximately 2-fold higher in the case of tRNAAlaGPsiU than tRNAAlaGUU. These findings imply that Psi35 of echinoderm mt tRNAAsn actually serves to decode the unusual asparagine codon AAA, resulting in the alteration of the genetic code in echinoderm mitochondria.
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PMID:The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria. 1007

We describe here a novel allele, HLA-Cw*1507, identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT). Cw*1507 is similar to Cw*1502 with differences at nucleotide positions 302 (A to G) and 312 (A to C) in exon 2. The substitutions observed in Cw*1507, change codon 77 from AAC (asparagine) to AGC (serine) and codon 80 from AAA (lysine) to AAC (asparagine), compared to Cw*1502. Residues 77 and 80 of HLA-C alleles are located in the alpha 1 domain, where they can influence interaction between antigenic peptides and the T-cell receptor. Also, the dimorphism at these residues from asparagine and lysine to serine and asparagine, respectively, are known to modulate interaction with the natural killer (NK) cell killer inhibitory receptor (KIR). The new HLA-Cw*1507, together with Cw*1502, represents the fourth pair of HLA-C alleles differing only at the KIR-related dimorphic codons 77 and 80.
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PMID:Identification of a new variant, HLA-Cw*1507, differing from Cw*1502 only at the KIR-related dimorphism of codons 77 and 80. 1037 48

E6 and E7 genes of human papilloma virus type 18 have been subcloned from plasmid pC7, carrying an insert of DNA from squamous cell carcinoma of cervix. Both genes in comparison to prototype variant contain one mutation that changes asparagine to leucine. In the case of E6 gene this mutation is mapped in codon 129, in the case of E7 the same change AAC to AAA mapped in codon 92. In addition both genes contain few point mutations that do not change the aminoacid sequences of the protein. Two mutants of E7 gene have been constructed by site directed mutagenesis based on PCR technology-one in codon 10 (change Asp to Asn) and one in codon 24 (change Asp to Gly). The first type of mutation did not influence the transformation potential of the E7 gene in comparison to the parental one with mutation in codon 92. The mutation in codon 24 (region responsible for the interaction with Rb protein) eliminate the transformation potential of the gene. The cells transformed with E7 mutants in codons 10 and 92 were tumorigenic for syngenic rats.
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PMID:Cloning of E6 and E7 genes of human papilloma virus type 18 and transformation potential of E7 gene and its mutants. 1040

Paraffin embedded tissues from twenty-two Thai patients with non-small cell lung cancer were studied for p53 gene mutations in exon 5 to 8 using polymerase chain reaction and single-stranded conformation polymorphism (PCR-SSCP) followed by thermal cycle sequencing. Results showed that point mutations in this region of p53 gene were present in 3 cases. One harboured the base change from GAC to AAC at codon 281, changing amino acid from aspartic acid to asparagine, whilst the other cases were transversion of AAA (lysine) to ACA (threonine) at codon 292. All subjects with p53 mutation had a past history of tobacco smoking.
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PMID:p53 gene mutations in non-small cell lung cancer from Thai patients. 1041 Apr 79

The flatworm mitochondrial genetic code, which has been used for all species of the Platyhelminthes, is mainly characterized by AUA codon for isoleucine, AAA codon for asparagine and UAA codon for tyrosine. In eight species of cestodes (Echinococcus multilocularis, Echinococcus granlosus, Taenia solium Taenia saginata, Taenia hydatigena, Taenia crassiceps, Hymenolepis nama and Mesocestoides corti), the cytochrome c oxidase subunit I (COI) genes were partially sequenced to verify this genetic code. Comparison of the COI-encoding nucleotide sequences with those of human, sea urchin, fruit fly, nematode and yeast indicated that the assignments of AUA and AAA codons are adequate for cestodes. In addition, the nucleotide sequences of ATPase subunit 6 (ATP6) gene and its flanking region were compared to examine initiation and stop codons. In the related species of T. solium and T. saginata, the deduced amino acid sequences of ATP6 were homogeneous; however, the conversion of initiation codon AUG into GUG was observed in T. saginata. We also found the similar conversion in T. crassiceps. The C-terminal sequences of putative ATP6 proteins were highly conserved among the eight species and the stop codon UAG was altered to UAA in all Taenia species. The features of the gene-junctional region between NADH dehydrogenase subunit 4 (ND4) and glutamine tRNA (tRNAGln) genes also supported that UAA serves as a stop codon. Based on these results, we propose that the flatworm mitochondrial code should be modified for cestodes, particularly, in an initiating methionine codon (GUG) and a terminating codon (UAA).
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PMID:Mitochondrial genetic code in cestodes. 1116 47


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