Alternative titles; symbols
HGNC Approved Gene Symbol: MGAT1
Cytogenetic location: 5q35.3 Genomic coordinates (GRCh38): 5:180,784,780-180,815,616 (from NCBI)
There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. One of these, UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-T I; EC 2.4.1.101), is a medial-Golgi enzyme essential for the synthesis of hybrid and complex N-glycans. Kumar and Stanley (1989) identified the human gene encoding N-acetylglucosaminyltransferase I by complementation of the glycosylation defect in the Lec1 Chinese hamster ovary (CHO) cell mutant. Kumar et al. (1990) cloned MGAT1 cDNA. The overall features of the cDNA and deduced protein sequence (445 amino acids) were typical of other Golgi transferases that are type II transmembrane proteins.
On Northern blots, Yip et al. (1997) found that GlcNAc-T I is expressed as 2 mRNAs of 3.1 and 2.7 to 3.0 kb in all tissues tested, although only the 3.1-kb mRNA is seen in brain, and expression levels are low.
Hull et al. (1991) isolated 2 overlapping genomic DNA clones which span 18 kb containing the single 2.5-kb exon for GlcNAc-T I. The exon includes most of the 5-prime untranslated region, the complete coding sequence (1,335 bases, 445 amino acids), and the complete 3-prime untranslated region. Southern blot analysis indicated that the gene (symbolized GLCT1) exists in single copy in the human genome.
Yip et al. (1997) found that exon 1 of the GlcNAc-T I gene contains multiple transcription start sites.
Pownall et al. (1992) demonstrated that the sequence of the mouse Mgat1 gene is highly conserved with respect to the human and rabbit homologs and exists as a single protein-encoding exon.
By study of human-hamster somatic cell hybrids, Hull et al. (1991) mapped the GLCT1 gene to chromosome 5.
Pownall et al. (1992) mapped the gene to mouse chromosome 11, closely linked to the gene encoding IL3 (147740), by the analysis of multilocus interspecies backcrosses. Thus, the human gene may be in the same area as IL3, i.e., 5q23-q31.
Kumar et al. (1992) mapped the MGAT1 gene to 5q31.2-q31.3 by in situ hybridization. Tan et al. (1995) reported that the MGAT1 gene maps to 5q35 by fluorescence in situ hybridization. In an erratum, Haley et al. (1999) stated that by use of more sensitive FISH technology than that used in their 1992 report (Kumar et al., 1992), they confirmed the assignment of the MGAT1 gene to 5q35 as reported by Tan et al. (1995).
Ioffe and Stanley (1994) produced transgenic mice lacking Mgat1. Homozygous mutant mice died between 9.5 and 10.5 days of development and were developmentally retarded, especially in neural tissue. Metzler et al. (1994) obtained similar results, finding that neural tube formation, vascularization, and left-right asymmetry formation were impaired in homozygous mutant mouse embryos.
Puthalakath et al. (1996) demonstrated that the CHO Lec1 mutation is a point mutation. Lec1 mutant cells have a cys123-to-arg substitution that results in a complete loss of enzyme activity. Two other point mutations in the Lec1 mutant, gln339 to arg and lys401 to arg, have no apparent effect on catalytic activity.
Haley, L. L., Eddy, R. L., Chen, W., Stanley, P., Shows, T. B. Erratum to Cloning and the expression of the murine gene and chromosomal location of the human gene encoding N-acetylglucosaminyltransferase I by Kumar et al. Glycobiology 9: ix only, 1999.
Hull, E., Sarkar, M., Spruijt, M. P. N., Hoppener, J. W. M., Dunn, R., Schachter, H. Organization and localization to chromosome 5 of the human UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase 1 gene. Biochem. Biophys. Res. Commun. 176: 608-615, 1991. [PubMed: 1827260] [Full Text: https://doi.org/10.1016/s0006-291x(05)80227-x]
Ioffe, E., Stanley, P. Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates. Proc. Nat. Acad. Sci. 91: 728-732, 1994. [PubMed: 8290590] [Full Text: https://doi.org/10.1073/pnas.91.2.728]
Kumar, R., Stanley, P. Transfection of a human gene that corrects the Lec1 glycosylation defect: evidence for transfer of the structural gene for N-acetylglucosaminyltransferase I. Molec. Cell. Biol. 9: 5713-5717, 1989. Note: Erratum: Molec. Cell. Biol. 10: 3857 only, 1990. [PubMed: 2531285] [Full Text: https://doi.org/10.1128/mcb.9.12.5713-5717.1989]
Kumar, R., Yang, J., Eddy, R. L., Byers, M. G., Shows, T. B., Stanley, P. Cloning and expression of the murine gene and chromosomal location of the human gene encoding N-acetylglucosaminyltransferase I. Glycobiology 2: 383-393, 1992. Note: Erratum: Glycogiology 9: ix only, 1999. [PubMed: 1421759] [Full Text: https://doi.org/10.1093/glycob/2.4.383]
Kumar, R., Yang, J., Larsen, R. D., Stanley, P. Cloning and expression of N-acetylglucosaminyltransferase I, the medial Golgi transferase that initiates complex N-linked carbohydrate formation. Proc. Nat. Acad. Sci. 87: 9948-9952, 1990. [PubMed: 1702225] [Full Text: https://doi.org/10.1073/pnas.87.24.9948]
Metzler, M., Gertz, A., Sarkar, M., Schachter, H., Schrader, J. W., Marth, J. D. Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development. EMBO J. 13: 2056-2065, 1994. [PubMed: 8187759] [Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06480.x]
Pownall, S., Kozak, C. A., Schappert, K., Sarkar, M., Hull, E., Schachter, H., Marth, J. D. Molecular cloning and characterization of the mouse UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I gene. Genomics 12: 699-704, 1992. [PubMed: 1533386] [Full Text: https://doi.org/10.1016/0888-7543(92)90297-6]
Puthalakath, H., Burke, J., Gleeson, P. A. Glycosylation defect in lec1 Chinese hamster ovary mutant is due to a point mutation in N-acetylglucosaminyltransferase 1 gene. J. Biol. Chem. 271: 27818-27822, 1996. [PubMed: 8910379] [Full Text: https://doi.org/10.1074/jbc.271.44.27818]
Tan, J., D'Agostaro, G. A. F., Bendiak, B., Reck, F., Sarkar, M., Squire, J. A., Leong, P., Schachter, H. The human UDP-N-acetylglucosamine:alpha-6-D-mannoside-beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2): cloning of genomic DNA, localization to chromosome 14q21, expression in insect cells and purification of the recombinant protein. Europ. J. Biochem. 231: 317-328, 1995. [PubMed: 7635144] [Full Text: https://doi.org/10.1111/j.1432-1033.1995.tb20703.x]
Yip, B., Chen, S.-H., Mulder, H., Hoppener, J. W. M., Schachter, H. Organization of the human beta-1,2-N-acetylglucosaminyltransferase I gene (MGAT1), which controls complex and hybrid N-glycan synthesis. Biochem. J. 321: 465-474, 1997. [PubMed: 9020882] [Full Text: https://doi.org/10.1042/bj3210465]