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Gene Review

Ggta1  -  glycoprotein galactosyltransferase alpha 1, 3

Mus musculus

Synonyms: AW108479, GALT, Gal, Galactosyltransferase, Ggta, ...
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Disease relevance of Ggta1


High impact information on Ggta1


Chemical compound and disease context of Ggta1

  • An ascending E. coli urinary tract infection model was established in the 16-wk-old female BALB/c mouse to compare the pathogenic significance of MS and Gal-Gal pili and their efficacy as vaccines for the prevention of pyelonephritis [8].
  • Enzymatically active GalTase could be recovered from an affinity column of C6 coupled to Sepharose 4B following application of a cell extract from a human colon cancer cell line, confirming that the mAb is directed against GalTase [9].
  • It was of interest to test whether inhibition of metastatic properties of BL6 melanoma cells is specifically associated with the appearance of the terminal alpha-Gal or whether capping N-acetyllactosamine with another oligosaccharide would also affect the metastatic properties of BL6 melanoma cells [10].
  • UDP-galactose:ceramide galactosyltransferase activity was assayed in the spinal cord and kidney of the recently discovered neurological mutant, the twitcher mouse, which is an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease) [11].
  • Despite the presence of galactose and its metabolites in tissues and urine and impaired ability to oxidize the sugar, the GALT-deficient animals are indistinguishable from normal animals and do not exhibit the phenotype of humans with GALT-deficiency galactosemia [12].

Biological context of Ggta1

  • These observations indicate that the Gal alpha 1-->3Gal moiety is not essential to sperm-oocyte interactions leading to fertilization or to essentially normal development [13].
  • Gene for murine alpha 1----3-galactosyltransferase is located in the centromeric region of chromosome 2 [14].
  • The crystal structure of the catalytic domain of substrate-free bovine alpha3GalT, solved and refined to 2.3 A resolution, has a globular shape with an alpha/beta fold containing a narrow cleft on one face, and shares a UDP-binding domain (UBD) with the recently solved inverting glycosyltransferases [15].
  • A cDNA library was constructed in a mammalian expression vector by using mRNA from a murine cell line known to express a UDPgalactose:beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase [(alpha 1-3)GT; EC] [16].
  • Repeated immunization of control KO mice with pig kidney membranes (PKM) expressing many alpha-gal epitopes induces an extensive anti-Gal antibody response against this epitope [17].

Anatomical context of Ggta1


Associations of Ggta1 with chemical compounds

  • alpha1,3-galactosyltransferase (alpha3GalT, EC is a Golgi-resident, type II transmembrane protein that transfers galactose from UDP-alpha-galactose to the terminal N:-acetyllactosamine unit of glycoconjugate glycans, producing the Galalpha1,3Galbeta1,4GlcNAc oligosaccharide structure present in most mammalian glycoproteins [15].
  • Biochemical analysis confirmed that this enzyme catalyzes a transglycosylation reaction between UDP-Gal and Gal(beta 1-4)GlcNAc to form Gal(alpha 1-3)Gal(beta 1-4)GlcNAc [16].
  • In this location, GalTase could conceivably impede zona penetration by binding to N-acetylglucosamine residues exposed on zona pellucida glycoproteins [18].
  • The addition of an alpha 3-fucosyl residue to each of these two competitive inhibitors, forming Gal beta 1,4[Fuc alpha 1,3] GlcNAc beta 1,4GlcNAc or Gal alpha 1,3Gal beta 1, 4[Fuc alpha 1,3]Glc NAc, resulted in ligands with 85- and 12-fold higher affinities for sperm, respectively (ED50 = 500 and 430 nM) [19].
  • To have a means for exploring this possibility and for studying the species and tissue distribution of this epitope we have raised a monoclonal antibody (Gal-13) which specifically binds to glycoconjugates with a nonreducing terminal Gal alpha 1-3Gal disaccharide [20].

Physical interactions of Ggta1


Regulatory relationships of Ggta1

  • A membrane fraction isolated from lactating murine mammary tissue and enriched for the Golgi membrane marker enzyme galactosyltransferase exhibited Ca2+-stimulated ATPase activity (Ca-ATPase) in 20 microM-free Mg2+ and 10 microM-MgATP, with an apparent Km for Ca2+ of 0.8 microM [22].
  • In both the Twitcher and the control groups the galactosyltransferase activity rapidly increased up to 20-25 DIV and then declined [23].
  • Expression of GnT-III also suppressed the antigenicity of MEC to human natural antibodies as shown by binding of Griffonia simplicifolia 1 isolectin (GS1B4 lectin) to the alpha-Gal epitope [24].

Other interactions of Ggta1


Analytical, diagnostic and therapeutic context of Ggta1


  1. Alterations of cell surface carbohydrates and inhibition of metastatic property of murine melanomas by alpha 1,3 galactosyltransferase gene transfection. Gorelik, E., Duty, L., Anaraki, F., Galili, U. Cancer Res. (1995) [Pubmed]
  2. Retinoic acid-induced differentiation of the mouse teratocarcinoma cell line F9 is accompanied by an increase in the activity of UDP-galactose: beta-D-galactosyl-alpha 1,3-galactosyltransferase. Cummings, R.D., Mattox, S.A. J. Biol. Chem. (1988) [Pubmed]
  3. Distribution of, and immune response to, chicken anti-alpha Gal immunoglobulin Y antibodies in wild-type and alpha Gal knockout mice. Walsh, W.E., Anderson, B.E., Ivancic, D., Zhang, Z., Piccini, J.P., Rodgers, T.G., Pao, W., Fryer, J.P. Immunology (2000) [Pubmed]
  4. Suppression of Lewis lung tumor development in alpha 1,3 galactosyltransferase knock-out mice. Posekany, K.J., Pittman, H.K., Swanson, M.S., Haisch, C.E., Verbanac, K.M. Anticancer Res. (2004) [Pubmed]
  5. Temporally specific involvement of cell surface beta-1,4 galactosyltransferase during mouse embryo morula compaction. Bayna, E.M., Shaper, J.H., Shur, B.D. Cell (1988) [Pubmed]
  6. Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Fan, J.Q., Ishii, S., Asano, N., Suzuki, Y. Nat. Med. (1999) [Pubmed]
  7. Activation of a G protein complex by aggregation of beta-1,4-galactosyltransferase on the surface of sperm. Gong, X., Dubois, D.H., Miller, D.J., Shur, B.D. Science (1995) [Pubmed]
  8. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c mice. Gal-Gal pili immunization prevents Escherichia coli pyelonephritis in the BALB/c mouse model of human pyelonephritis. O'Hanley, P., Lark, D., Falkow, S., Schoolnik, G. J. Clin. Invest. (1985) [Pubmed]
  9. Characterization of monoclonal antibodies to serum galactosyltransferase. Podolsky, D.K., Isselbacher, K.J. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  10. Reduction of metastatic properties of BL6 melanoma cells expressing terminal fucose(alpha)1-2-galactose after alpha1,2-fucosyltransferase cDNA transfection. Gorelik, E., Xu, F., Henion, T., Anaraki, F., Galili, U. Cancer Res. (1997) [Pubmed]
  11. Glycosylceramide synthesis in the developing spinal cord and kidney of the twitcher mouse, an enzymatically authentic model of human Krabbe disease. Kodama, S., Igisu, H., Siegel, D.A., Suzuki, K. J. Neurochem. (1982) [Pubmed]
  12. Galactose metabolism by the mouse with galactose-1-phosphate uridyltransferase deficiency. Ning, C., Reynolds, R., Chen, J., Yager, C., Berry, G.T., McNamara, P.D., Leslie, N., Segal, S. Pediatr. Res. (2000) [Pubmed]
  13. Oocyte Gal alpha 1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. Thall, A.D., Malý, P., Lowe, J.B. J. Biol. Chem. (1995) [Pubmed]
  14. Gene for murine alpha 1----3-galactosyltransferase is located in the centromeric region of chromosome 2. Joziasse, D.H., Shaper, N.L., Shaper, J.H., Kozak, C.A. Somat. Cell Mol. Genet. (1991) [Pubmed]
  15. Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases. Gastinel, L.N., Bignon, C., Misra, A.K., Hindsgaul, O., Shaper, J.H., Joziasse, D.H. EMBO J. (2001) [Pubmed]
  16. Isolation of a cDNA encoding a murine UDPgalactose:beta-D-galactosyl- 1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase: expression cloning by gene transfer. Larsen, R.D., Rajan, V.P., Ruff, M.M., Kukowska-Latallo, J., Cummings, R.D., Lowe, J.B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  17. Tolerance induction to a mammalian blood group-like carbohydrate antigen by syngeneic lymphocytes expressing the antigen. Ogawa, H., Yin, D.P., Shen, J., Galili, U. Blood (2003) [Pubmed]
  18. Sperm require beta-N-acetylglucosaminidase to penetrate through the egg zona pellucida. Miller, D.J., Gong, X., Shur, B.D. Development (1993) [Pubmed]
  19. Murine sperm-zona binding, a fucosyl residue is required for a high affinity sperm-binding ligand. A second site on sperm binds a nonfucosylated, beta-galactosyl-capped oligosaccharide. Johnston, D.S., Wright, W.W., Shaper, J.H., Hokke, C.H., Van den Eijnden, D.H., Joziasse, D.H. J. Biol. Chem. (1998) [Pubmed]
  20. Identification of erythrocyte Gal alpha 1-3Gal glycosphingolipids with a mouse monoclonal antibody, Gal-13. Galili, U., Basbaum, C.B., Shohet, S.B., Buehler, J., Macher, B.A. J. Biol. Chem. (1987) [Pubmed]
  21. Altering the expression of cell surface beta 1,4-galactosyltransferase modulates cell growth. Hinton, D.A., Evans, S.C., Shur, B.D. Exp. Cell Res. (1995) [Pubmed]
  22. A Ca2+-stimulated adenosine triphosphatase in Golgi-enriched membranes of lactating murine mammary tissue. Watters, C.D. Biochem. J. (1984) [Pubmed]
  23. The twitcher mouse: myelinogenesis in organotypic culture. Bourque, E.A., Bornstein, M.B., Peterson, E.R., Suzuki, K. Brain Res. (1983) [Pubmed]
  24. Reduction of the Gal-alpha1,3-Gal epitope of mouse endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene. Chung, T.W., Kim, K.S., Kim, C.H. Mol. Cells (2003) [Pubmed]
  25. Reduced galactosyltransferase mRNA levels are associated with the agalactosyl IgG found in arthritis-prone MRL-lpr/lpr strain mice. Jeddi, P.A., Lund, T., Bodman, K.B., Sumar, N., Lydyard, P.M., Pouncey, L., Heath, L.S., Kidd, V.J., Delves, P.J. Immunology (1994) [Pubmed]
  26. Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences. Singer, I.I., Kawka, D.W., DeMartino, J.A., Daugherty, B.L., Elliston, K.O., Alves, K., Bush, B.L., Cameron, P.M., Cuca, G.C., Davies, P. J. Immunol. (1993) [Pubmed]
  27. Beta-1,4-galactosyltransferase expression during spermatogenesis: stage-specific regulation by t alleles and uniform distribution in + -spermatids and t-spermatids. Pratt, S.A., Shur, B.D. Dev. Biol. (1993) [Pubmed]
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