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Cobalamin (vitamin B12) binding, phylogeny, and synteny of human transcobalamin.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2004 Nov 15; Vol. 431 (2), pp. 189-96. - Publication Year :
- 2004
-
Abstract
- Selected residues in a highly conserved 15-residue region, 174SVDTAAMAGLAFTC L188 of human transcobalamin (TC), a cobalamin (Cbl: vitamin B12) binding protein, were subjected to site-directed mutagenesis. The mutant constructs were expressed in TC-deficient fibroblasts or in vitro to assess the effect of these mutations on Cbl binding. Phylogenetic analyses and protein parsimony indicated that TC evolved earlier than other mammalian Cbl-binding proteins, intrinsic factor and haptocorrins, and divergence occurred between mouse/rat and human dispersing TC gene to different chromosomes. These studies show that (a) two of the three polar residues, S174, T177, or D176 and two of the three conserved alanine residues, A179 and A184 present in the 15-residue evolutionary conserved region are essential for Cbl-binding by human TC, and (b) TC gene is transferred in a syntenic manner to different chromosomes, at least before the divergence of mouse/rat and human.
- Subjects :
- Alanine metabolism
Amino Acid Sequence
Animals
Cells, Cultured
Chromosomes
Chromosomes, Human, Pair 22
Conserved Sequence
Culture Media
Evolution, Molecular
Fibroblasts metabolism
Humans
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Precipitin Tests
Protein Processing, Post-Translational
Protein Structure, Tertiary
Rats
Sequence Homology, Amino Acid
Transcobalamins chemistry
Phylogeny
Synteny
Transcobalamins genetics
Transcobalamins metabolism
Vitamin B 12 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9861
- Volume :
- 431
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 15488467
- Full Text :
- https://doi.org/10.1016/j.abb.2004.08.011