Alternative titles; symbols
HGNC Approved Gene Symbol: OGA
Cytogenetic location: 10q24.32 Genomic coordinates (GRCh38) : 10:101,784,450-101,818,444 (from NCBI)
The dynamic modification of cytoplasmic and nuclear proteins by O-linked N-acetylglucosamine (O-GlcNAc) addition and removal on serine and threonine residues is catalyzed by OGT (300255), which adds O-GlcNAc, and MGEA5, a glycosidase that removes O-GlcNAc modifications (Gao et al., 2001).
By screening a meningioma expression library with autologous serum, Heckel et al. (1998) identified 4 cDNA clones representing a novel gene, which they designated meningioma-expressed antigen-5, with striking homology to C. elegans hyaluronidase. MGEA5 was noted to have hyaluronidase activity, but was otherwise not characterized.
By sequencing randomly selected cDNAs corresponding to relatively long transcripts from human brain, Ishikawa et al. (1998) isolated an MGEA5 cDNA, which they designated KIAA0679, encoding a deduced 767-amino acid protein. RT-PCR detected high MGEA5 expression in all tissues examined.
By searching databases for sequences similar to bovine O-GlcNAcase, followed by 5-prime RACE of a brain cDNA library, Gao et al. (2001) cloned human MGEA5, or O-GlcNAcase. The deduced 916-amino acid protein has an N-terminal domain of about 400 amino acids and a C-terminal domain of about 350 amino acids that are highly conserved in vertebrate and invertebrate homologs. The central region of about 150 amino acids is highly variable. Northern blot analysis detected O-GlcNAcase in all human tissues examined, with highest expression in brain, followed by placenta and pancreas, and lowest expression in lung and liver.
Comtesse et al. (2001) identified a splice variant of MGEA5, which they called MGEA5s, that includes part of intron 10 and has an alternative stop codon and alternative polyadenylation signal. The deduced 677-amino acid protein lacks the C-terminal acetyltransferase domain. Both MGEA5 and MGEA5s contain several possible phosphorylation sites, N-glycosylation sites, and O-glycosylation sites. Western blot analysis of a fractionated human glioblastoma cell line detected MGEA5 at an apparent molecular mass of 130 kD in the cytoplasmic fraction, and MGEA5s at an apparent molecular mass of 75 kD in the nuclear fraction. A fraction containing membrane and cytoskeletal components showed the 130-kD protein. Toleman et al. (2004) identified a variant of rat Mgea5, which they called Ncoat, that encodes a protein with the acetyltransferase domain, but lacking the O-GlcNAcase domain.
Gao et al. (2001) demonstrated that COS-7 cells overexpressing human O-GlcNAcase showed elevated O-GlcNAcase activity. Recombinant human O-GlcNAcase displayed properties distinct from lysosomal beta-hexosaminidase (see HEXA; 606869), with distinct substrate preference and inhibitor sensitivity. O-GlcNAcase had a pH optimum of 5.7 to 7.0 and retained significant activity up to pH 8.0. It showed strict substrate specificity for beta-linked GlcNAc, and it cleaved GlcNAc attached to a test peptide.
Toleman et al. (2004) demonstrated that rodent Ncoat, when expressed in a mammalian system but not in bacteria, possessed acetyltransferase activity for a synthetic histone substrate, free core histones, and oligonucleosomal substrates. Deletion analysis indicated that the C-terminal third of Ncoat had histone acetyltransferase activity. Toleman et al., 2004 suggested that NCOAT may play a dual role in gene expression by removing O-GlcNAc modification from activators, while adding acetyl groups to histones.
Comtesse et al. (2001) determined that the MGEA5 gene contains 16 exons and spans over 34 kb.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the MGEA5 gene to chromosome 10. By somatic cell hybridization and FISH, Heckel et al. (1998) mapped the gene to 10q24.1-q24.3.
Forsythe et al. (2006) created a strain of C. elegans with knockout of Oga1, the nematode homolog of Mgea5. Oga1 knockout altered serine- and threonine-phosphoprotein profiles and increased GSK3B (605004) levels. Mutant worms showed elevated stores of glycogen and trehalose and decreased lipid storage.
Comtesse, N., Maldener, E., Meese, E. Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a beta-N-acetylglucosaminidase. Biochem. Biophys. Res. Commun. 283: 634-640, 2001. [PubMed: 11341771] [Full Text: https://doi.org/10.1006/bbrc.2001.4815]
Forsythe, M. E., Love, D. C., Lazarus, B. D., Kim, E. J., Prinz, W. A., Ashwell, G., Krause, M. W., Hanover, J. A. Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. Proc. Nat. Acad. Sci. 103: 11952-11957, 2006. [PubMed: 16882729] [Full Text: https://doi.org/10.1073/pnas.0601931103]
Gao, Y., Wells, L., Comer, F. I., Parker, G. J., Hart, G. W. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic, beta-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276: 9838-9845, 2001. [PubMed: 11148210] [Full Text: https://doi.org/10.1074/jbc.M010420200]
Heckel, D., Comtesse, N., Brass, N., Blin, N., Zang, K. D., Meese, E. Novel immunogenic antigen homologous to hyaluronidase in meningioma. Hum. Molec. Genet. 7: 1859-1872, 1998. [PubMed: 9811929] [Full Text: https://doi.org/10.1093/hmg/7.12.1859]
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 169-176, 1998. [PubMed: 9734811] [Full Text: https://doi.org/10.1093/dnares/5.3.169]
Toleman, C., Paterson, A. J., Whisenhunt, T. R., Kudlow, J. E. Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J. Biol. Chem. 279: 53665-53673, 2004. [PubMed: 15485860] [Full Text: https://doi.org/10.1074/jbc.M410406200]