title: gamma -Glutamyl carboxylation: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates.
abstract: The posttranslational gamma-carboxylation of glutamate residues in secreted proteins to gamma-carboxyglutamate is carried out by the vitamin K-dependent enzyme gamma-glutamyl carboxylase. gamma-Carboxylation has long been thought to be a biochemical specialization of vertebrates, essential for blood clotting. Recently, a gamma-carboxylase was shown to be expressed in Drosophila, although its function remains undefined in this organism. We have characterized both cDNA and genomic clones for the gamma-glutamyl carboxylase from the marine mollusc, Conus, the only nonvertebrate organism for which gamma-carboxyglutamate-containing proteins have been biochemically and physiologically characterized. The predicted amino acid sequence has a high degree of sequence similarity to the Drosophila and vertebrate enzymes. Although gamma-carboxylases are highly conserved, the Conus and mammalian enzymes have divergent substrate specificity. There are striking parallels in the gene organization of Conus and human gamma-carboxylases. Of the 10 Conus introns identified, 8 are in precisely the same position as the corresponding introns in the human enzyme. This remarkable conservation of intron/exon boundaries reveals that an intron-rich gamma-carboxylase was present early in the evolution of the animal phyla; although specialized adaptations in mammals and molluscs that require this extracellular modification have been identified, the ancestral function(s) and wider biological roles of gamma-carboxylation still need to be defined. The data raise the possibility that most introns in the genes of both mammals and molluscs antedate the divergence of these phyla.
authors.affiliation: Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112; and Cognetix, Inc., 401 Wakara Way no. 201, Salt Lake City, UT 84108.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bandyopadhyay
authors.forename: James E
authors.initials: JE
authors.lastname: Garrett
authors.forename: Reshma P
authors.initials: RP
authors.lastname: Shetty
authors.forename: Tyler
authors.initials: T
authors.lastname: Keate
authors.forename: Craig S
authors.initials: CS
authors.lastname: Walker
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001181:Arthropods; D019735:Carbon-Carbon Ligases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002816:Chordata, Nonvertebrate; D003001:Cloning, Molecular; D004330:Drosophila; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D008974:Mollusca; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012908:Snails
chemical_list: D011994:Recombinant Proteins; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase