O-LINKED GLCNAC TRANSFERASE IS A CONSERVED NUCLEOCYTOPLASMIC PROTEIN CONTAINING TETRATRICOPEPTIDE REPEATS

O-Linked GlcNAc addition and phosphorylation may compete for sites on nuclear pore proteins and transcription factors. We sequenced O-linked GlcNAc transferase from rabbit blood and identified the homologous Ca enorhabditis elegans transferase gene on chromosome III. We then isola ted C. elegans and human cDNAs encoding the transferase. The enzymes f rom the two species appear to be highly conserved; both contain multip le tetratricopeptide repeats and nuclear localization sequences, The C . elegans transferase accumulated in the nucleus and in perinuclear ag gregates in overexpressing transgenic lines, O-Linked GlcNAc transfera se activity was also elevated in HeLa cells transfected with the human cDNA. At least four human transcripts were observed in the tissues ex amined ranging in size from 4.4 to 9.3 kilobase pairs, The two largest transcripts (7.9 and 9.3 kilobase pairs) were enriched at least 12-fo ld in the pancreas, Based on its substrate specificity and molecular f eatures, we propose that O-linked GlcNAc transferase is part of a gluc ose-responsive pathway previously implicated in the pathogenesis of di abetes mellitus.