Missense mutations, protein

Monoclonal antibodies to mutated p53 proteins have been developed. The wild type of p53 is normally present in very small amounts that are not detected by immunohisto-chemistry, whereas the mutant protein accumulates to easily detectable levels. Overexpression of the mutant proteins has been detected in up to 70% of primary colorectal cancers. Overexpression of p53 in breast cancers is associated with poor prognosis, but this association is not as strong as the association with c-erhB-2. Up to 75% of small cell lung carcinomas appear to overexpress a mutant (missense mutation) protein. Finally, circulating antibodies to mutant p53 proteins have been found in sera from patients with breast and lung cancer and B-cell lymphomas. Tills antibody response may be useful in this subset of patients for monitoring for relapse. ... 

Genetic disorders of HDL metabolism have also resulted in greater understanding of the molecular regulation of HDL metabolism. Nonsense or missense mutations in apoA-I can result in substantially reduced HDL-C levels due to rapid catabolism of structurally abnormal or truncated apoA-I proteins. Tangier disease is a rare autosomal codominant disorder characterized by markedly low HDL-C and apoA-I levels and caused... 

Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E et al. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy evidence for a defect in protein trafficking. Hum Mol Genet 2000 9(8) 1209-1217. 

Goate,A., Chartier-Harlin,M. C.,Median,M. etal. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer s disease. Nature 349 704-706, 1991. 

Missense mutation This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene. 

Mitsiou and Stunnenberg, 2003). Moreover, enzyme-substrate interactions could be disrupted by missense mutations that are located throughout the protein. A clear example of this are the mutations in SRCl, which affect its interaction with CBP, but are located outside the CID region of SRCl (Rowan et al 2000 Wu et al., 2004) (see also above and Fig. lb). 

Missense mutations in the Notch3 gene cause CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lenkoencephalopathy). Notch is a type I integral membrane protein proteolytically processed in its extracellular domain by fnrin and the metalloproteinase knzbanian. The signal transduction cascade... 

VanWesenbeeck, L., Cleiren, E., Gram, J., Beals, R.K., Benichou, 0., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M.L., DeVernejonl, M-C., Bollerslev, J., and VanHnl, W. (2003) Six Novel Missense Mutations in the LDL Receptor-Related Protein 5 (LRP5) Gene in Different Conditions with an Increased Bone Density. American Journal of Human Genetlcsll, 763-771. 

Several missense mutations (le, at codons 12, 13, or 61) render the mutant protein Incapable of hydrolyzing bound GTP to GDP. 

Cafferkey, R. Young, P.R. McLaughlin, M.M. Bergsma, D.J. Koltin, Y. Sathe, G.M. Faucette, L. Eng, W.K. Johnson, R.K. Livi, G.P. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol. Cell. Biol., 13, 6012-6023 (1993)... 

Codons are composed of three nucleotide bases usually presented in Ihe mRNA language of A, G, C, and U. They are always written 5 —>3. Of the 64 possible three-base combinations, 61 code for the twenty common amino acids and three signal termination of protein synthesis (translation). Altering the nucleotide sequence in a codon can cause sient mutations (the altered codon also codes for the original amino acid), missense mutations (the altered codon codes for a different amino acid), or nonsense mutations (the altered codon is a termination... 

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