Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene.
O-Linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediates a novel hexosamine-dependent signal transduction pathway. Yet, little is known about the regulation of ogt gene expression in mammals. We report the sequence and characterization of the mouse ogt locus and provide a comparison with the human and rat ogt genes. The mammalian ogt genes are similar in structure and exhibit approximately 80% sequence identity. The mouse and human ogt genes contain two potential promoters producing four major transcripts. By analyzing 56 human cDNA clones and other existing expressed sequence tags, we found that at least three protein products differing at their amino terminus result from alternative splicing. We used OGT-specific antisera to demonstrate the presence of these isoforms in HeLa cells. The longest form is a nucleocytoplasmic OGT (ncOGT) with 12 tetratricopeptide repeats (TPRs); a shorter form of OGT encodes a mitochondrially sequestered enzyme with 9 TPRs and an N-terminal mitochondrion-targeting sequence (mOGT). An even shorter form of OGT (sOGT) contains only 2 TPRs. The genomic organization of OGT appears to be highly conserved throughout metazoan evolution. These results provide the basis for a more detailed analysis of the significance and regulation of the nucleocytoplasmic and mitochondrial isoforms of OGT in mammals.
Hanover
John A
JA
Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Building 8, Room 402, 8 Center Drive, MSC 0850, NIH, Bethesda, MD 20892-0850, USA. jah@helix.nih.gov
Yu
Song
S
Lubas
William B
WB
Shin
Sang Hoon
SH
Ragano-Caracciola
Maria
M
Kochran
Jarema
J
Love
Dona C
DC
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D002874:Chromosome Mapping; D003593:Cytoplasm / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D015183:Restriction Mapping
D007527:Isoenzymes; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase