Primary structure and expression analysis of humanUDP‐N‐acetyl‐glucosamine‐2‐epimerase/N‐acetylmannosamine kinase,the bifunctional enzyme in neuraminic acid biosynthesis¹

Abstract

N-Acetylneuraminic acid is a main constituent of glycoproteins and gangliosides. In many membrane-bound receptors it is the target for external stimuli. The key enzyme for its biosynthesis is the bifunctional enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase, catalysing the first two steps of the biosynthesis in the cytosol. The rat enzyme was previously isolated and characterised. In this report we present the corresponding human cDNA sequence, compare it with the primary structure of the rodent enzyme, and report the analysis of its expression in different human tissues and cell lines.

UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis

“…Although CpG methylation of the GNE gene was unequivocally shown only in lymphocytes, it is very likely, that the same mechanismoccurs in other tissues and contributes to tissue-specific adjustment of GNE expression. The non-coding part of human GNE exon 12 together with exon 13 form a non-coding 3′-end with an extraordinary lenght of more than 2000 bp in human transcripts [23]. However, GNE transcripts of other mammalian species do contain much shorter 3′-ends, as shown by Northern blot analysis [11, 22].…”

“…GNE mRNA is ubiquitously expressed in all organs and during all stages of development, as shown in Northern blot and in situ -hybridization experiments. However the major expression of GNE mRNA is found in liver [11, 22, 23], likely because liver is the organ with the highest biosynthesis rate of secreted sialylated glycoproteins (e.g. serum glycoproteins).…”

Identification of an Alu element‐mediated deletion in the promoter region of GNE in siblings with GNE myopathy

“…1999; Lucka et al. 1999). Sialic acids are negatively charged carbohydrate derivatives that are widely distributed across different tissues with distinctive roles in each cell type including cell proliferation, cell interaction, and immune defense (Varki and Varki 2007).…”

“…Total hGNE mRNA is highest in liver and placenta, while skeletal muscle has low expression (Lucka et al. 1999; Yardeni et al. 2011).…”

Safety and in vivo Expression of a GNE-Transgene: A Novel Treatment Approach for Hereditary Inclusion Body Myopathy-2

“…The GNE gene encodes the bifunctional enzyme uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) 2 epimerase/N acetyl-mannosamine (ManNAc) kinase (GNE/MNK) 9,10. This enzyme is ubiquitously expressed and catalyzes the first 2 steps of the sialic acid biosynthesis pathway 11.…”