Fig. 3.

GNE gene and protein structure. (A) Exon (boxes)-intron (lines) structures of the two major human GNE mRNA transcripts, formed by alternative splicing of N-terminal exons. mRNA variant 1 (the longest splice form) encodes the hGNE2 protein, and mRNA variant 2 encodes the hGNE1 protein. Colored boxes represent the open reading frame and functional domains (colors correspond with translated protein domains in (B)). White boxes represent untranslated regions (UTRs) and white dotted lined boxes the skipped exons of each transcript. (B) hGNE2 protein structure. Gray UF, unknown function; dark red, UDP-GlcNAc 2-epimerase enzymatic activity encoding domain; vertical lined, putative nuclear export signal (NES); dotted, experimental allosteric region (AR) for CMP-sialic acid binding; green, ManNAc kinase enzymatic activity encoding domain. Amino acid numbering of both hGNE1 and hGNE2 protein isoforms is indicated below the structure. (C) Location on the GNE protein of frequent GNE mutations associated (see Table 1 for details)