cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse.

We subcloned human and mouse full-length cDNAs of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT), which was designated GFAT2 (the previously reported GFAT was named GFAT1). Both the human and the mouse GFAT2 proteins deduced from their open reading frame sequences are composed of 682 amino acids of approximately 77.0 kDa. At the amino acid level, homologies between the human GFAT1 and GFAT2, between the mouse GFAT1 and GFAT2, and between the human GFAT2 and the mouse GFAT2 were 75.6, 74.7, and 97. 2%, respectively. Northern blot analysis using probe specific to human GFAT1 or GFAT2 showed that major transcripts were approximately 3.0 kb in both the human GFAT subtypes. The analysis also revealed different tissue distribution between GFAT1 and GFAT2: GFAT1 was more highly expressed in the placenta, pancreas, and testis than GFAT2; GFAT2 was expressed throughout the central nervous system, especially in the spinal cord, but GFAT1 expression was weak. The locus was mapped to human chromosome 5q and mouse chromosome 11, where a synteny between the two species has been known. GFAT2 can provide insights into understanding the roles of the hexosamine pathway in various tissues, particularly with the development of glucose toxicity and diabetes complications.