MOLECULAR-CLONING OF A 4TH MEMBER OF A HUMAN ALPHA(1,3)FUCOSYLTRANSFERASE GENE FAMILY - MULTIPLE HOMOLOGOUS SEQUENCES THAT DETERMINE EXPRESSION OF THE LEWIS-X, SIALYL LEWIS-X, AND DIFUCOSYL SIALYL LEWIS-X EPITOPES

We and others have previously described the isolation of three human alpha(1,3)fucosyltransferase genes which form the basis of a nascent glycosyltransferase gene family. We now report the molecular cloning and expression of a fourth homologous human alpha(1,3)fucosyltransferase gene. When transfected into mammalian cells, this fucosyltransferase gene is capable of directing expression of the Lewis x (Galbeta1-->4[Fucalpha1-->3] GlcNAc), sialyl Lewis x (NeuNAcalpha2-->3Galbeta1-->4 [Fucalpha1-->3]GlcNAc),and difucosyl sialyl Lewis x (NeuNAcalpha2-->3Galbeta1-->4[Fucalpha1-->3]GlcNAcbeta1-->3Galbeta1-->4[Fucalpha1-->3]GlcNAc) epitopes. The enzyme shares 85% amino acid sequence identity with Fuc-TIII and 89% identity with Fuc-TV but differs substantially in its acceptor substrate requirements. Polymerase chain reaction analyses demonstrate that the gene is syntenic to Fuc-TIII and Fuc-TV on chromosome 19. Southern blot analyses of human genomic DNA demonstrate that these four alpha(1,3)fucosyltransferase genes account for all DNA sequences that cross-hybridize at low stringency with the Fuc-TIII catalytic domain. Using similar methods, a catalytic domain probe from Fuc-TIV identifies a new class of DNA fragments which do not cross-hybridize with the chromosome 19 fucosyltransferase probes. These results extend the molecular definition of a family of human alpha(1,3)fucosyltransferase genes and provide tools for examining fucosyltransferase gene expression.