Molecular evolution of protein O-fucosyltransferase genes and splice variants

Abstract

O-Fucose has been described on both epidermal growth factor-like (EGF-like) repeats and Thrombospondin type 1 repeats (TSRs). The enzyme adding fucose to EGF-like repeats, protein O-fucosyltransferase 1 (Pofut1), is a soluble protein located in the lumen of endoplasmic reticulum (ER). A second protein O-fucosyltransferase, Pofut2, quite divergent from its homolog Pofut1, has recently been shown to O-fucosylate TSRs but not EGF-like repeats. To date, Pofut1 genes have only been characterized in human, mouse, and fly, and Pofut2 in mouse, fly, and partially in the nematode Caenorhabditis elegans. Here, we report cDNA sequences and genomic structures of bovine Pofut1 and Pofut2 genes and describe for the first time five alternative spliced transcripts for each gene. Only one transcript for both Pofut1 and Pofut2 encodes an active bovine O-fucosyltransferase. Variant transcript distribution was examined in 13 bovine tissues. Transcripts encoding active forms are ubiquitous, whereas other forms possess a more restricted tissue-expression profile. Sequence comparison and phylogenetic analyses revealed that both Pofut genes are present as a single copy in animal genomes, and their exon-intron organizations are conserved among vertebrates. The last common ancestor of all analyzed bilaterian species would be predicted to possess polyexonic Pofut genes in their genome.

Golgi Glycosylation

“…However, O-fucose glycans in Drosophila may have a glucuronic acid attached to the O-fucose (Aoki et al 2008), and there is no evidence for the addition of Gal or sialic acid to the GlcNAc (Xu et al 2007). C. elegans has protein O-fucosyltransferase 1 (Loriol et al 2006), but no close homologue of Fringe, the transferase that adds GlcNAc to Fucose-O-EGF (Bruckner et al 2000;Moloney et al 2000). The O-glucose glycans on EGF repeats appear to have emerged with Notch signaling in the metazoa (Acar et al 2008;Sethi et al 2010).…”

Protein O-Fucosyltransferase 1 Expression Impacts Myogenic C2C12 Cell Commitment via the Notch Signaling Pathway

“…A global transcriptomic approach based on glycogene analysis brought our attention to these enzymes in the context of the onset of myogenesis in C2C12 (30). The inverting glycosyltransferase Pofut1 was first characterized in mammalian CHO cells (31), and subsequent investigations demonstrated its presence in all principal metazoan genomes as a single-copy gene (32). Its expression is ubiquitous in the organism and confirmed to be present in skeletal muscles (22,32).…”

“…The inverting glycosyltransferase Pofut1 was first characterized in mammalian CHO cells (31), and subsequent investigations demonstrated its presence in all principal metazoan genomes as a single-copy gene (32). Its expression is ubiquitous in the organism and confirmed to be present in skeletal muscles (22,32). Unlike the Golgian fucosyltransferases involved in N-glycosylation, Pofut1 is an endoplasmic reticulum (ER)-resident glycoprotein (33).…”

Activity, Splice Variants, Conserved Peptide Motifs, and Phylogeny of Two New α1,3-Fucosyltransferase Families (FUT10 and FUT11)

“…Fucosyl residues in mammals are found linked to an oligosaccharide acceptor in ␣1,2-, ␣1,3-, ␣1,4-, and ␣1,6-orientations (6) or directly to serine or threonine as protein-O-fucosylations (7)(8)(9). The ␣1,2-fucosyltransferases (FUT1, FUT2, and Sec1) (10) and the ␣1,3/4-fucosyltransferases (FUT3-FUT7 and FUT9), resulting mainly from two rounds of whole genome duplication (11), are implicated in terminal fucosylations (12,13), and they are encoded by monoexonic genes (1).…”