Human Molecular Genetics, Vol 5, 1851-1858, Copyright © 1996 by Oxford University Press
YN Li, S Gulati, PJ Baker, LC Brody, R Banerjee and WD Kruger
Elevated levels of plasma homocysteine is a risk factor in both birth
defects and vascular disease. Methionine synthase (MS) is a cobalamin
dependent enzyme which catalyzes methylation of homocysteine to methionine.
Impaired MS activity is expected to lead to increased levels of plasma
homocysteine. In addition, defects in this gene may underlie the
methionine-dependence observed in a number of human tumor cell lines. We
describe here the isolation and characterization of the human MS cDNA. It
contains an open reading frame of 3798 nucleotides encoding a protein of
1265 amino acids with a predicted molecular mass of 140 kDa. The amino acid
sequence of the human MS is 55% identical with that of the Escherichia coli
enzyme (METH) and 64% identical with the predicted Caenorhabditis elegans
enzyme. Seven peptide sequences derived from purified porcine MS have
substantial similarity to the human protein. Northern analysis indicates
that the MS RNA is present in a wide variety of tissues. We have mapped the
human gene to chromosomal location 1q43, a region found monosomic in
individuals with deletion 1q syndrome. The isolation of the MS cDNA will
now allow the direct determination of whether mutations in this gene
contribute to folate-related neural tube defects, cardiovascular diseases,
and birth defects.
ARTICLES
Cloning, mapping and RNA analysis of the human methionine synthase gene
Division of Population Science, Fox Chase Cancer Center, Philadelphia, USA.
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