Deduction and exploration of the evolution and function of vertebrate GFPT family.

Background: Glutamine-fructose-6-phosphate aminotransferase (GFPT) is a key factor in the hexosamine metabolism pathway. It regulates the downstream factor O-GlcNAc to change cell function and plays an important role in the metabolism and immune process of tissues and organs. However, the evolutionary relationship of GFPT family proteins in vertebrates has not been elucidated.

Objective: To deduce and explore the evolution and function of vertebrate GFPT family.

Methods: 18 GFPT sequences were obtained from Homo sapiens (H. sapiens), Trachypithecus francoisi (T. francoisi), Mus musculus (M. musculus), Rattus norvegicus (R. norvegicus), Gallus gallus (G. gallus), Zootoca vivipara (Z. vivipara), Xenopus tropicalis (X. tropicalis), Danio rerio (D. rerio), Rhincodon typus (R. typus), Plasmodium relictum from National Center for Biotechnology Information (NCBI). The physical and chemical characteristics and molecular evolution of GFPT family proteins and nucleic acid sequences were analyzed by ClustalX2, Gene Doc, MEGA-X, SMART, Datamonkey, R etc. RESULTS: Based on the neighbor-joining (NJ) phylogenetic tree and evolution fingerprints, GFPT family members of vertebrates can be divided into two groups: the GFPT1 group and the GFPT2 group. Seven positive selection sites were identified by IFEL and integrated methods mixed effects model of evolution (MEME) and fixed effects likelihood (REL). Finally, we predicted 28 phosphorylation sites and 18 ubiquitousness sites in the human GFPT1 sequence, 10 phosphorylation sites, and five ubiquitousness sites in GFPT2. Gene ontology (GO) analyzes the protein molecules and KEGG signaling pathways of vertebrates interacting with GFPT family proteins.

Conclusions: Our work confirmed that higher animals GFPT family may have differentiated GFPT1 and GFPT2, which meets their own functional needs. This knowledge answers the question what the origin and evolution of GFPT family in vertebrates and provided the basis for disease treatment and function research of GFPT protein.