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Gene Review

Gla  -  galactosidase, alpha

Mus musculus

Synonyms: Ags, Alpha-D-galactosidase A, Alpha-D-galactoside galactohydrolase, Alpha-galactosidase A, Melibiase
 
 
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Disease relevance of Gla

  • To determine if mice genetically deficient in Gla are susceptible to vascular thrombosis, a photochemical carotid injury model was used to induce occlusive thrombosis [1].
  • These studies reveal a potent vascular prothrombotic phenotype in Gla-deficient mice and suggest that antithrombotic therapies as well as therapies designed to reduce the vascular accumulation of Gb3 may have beneficial effects on thrombotic complications in patients with Fabry disease [1].
  • Osteocalcin-knockout mice develop hyperostosis, suggesting that the Gla-containing osteocalcin promotes normal bone mineralization [2].
  • This newly developed Gla-OC specific EIA may be useful for the diagnosis of metabolic bone disease and ectopic calcification [3].
  • This approach should be feasible for designing peptide analogues that can be tested for therapeutic efficacy in human autoimmune diseases in which the pathogenic Ags are known and TCR use is diverse [4].
 

Psychiatry related information on Gla

  • In the search for subunit vaccines that are able to induce the type of sterile, protective immunity achieved by irradiated sporozoites, there is increasing evidence that defense mechanisms directed at the intrahepatic stage and Ags expressed at this stage are critical [5].
 

High impact information on Gla

  • All members of this family have glutamic acid residues modified to gamma-carboxyglutamic acids (Gla) by a specific gamma-carboxylase using vitamin K as a cofactor [6].
  • Acquired immunity depends on proliferation and differentiation of antigen (Ag)-specific B cells in germinal centers (GCs) of lymphoid follicles in response to T cell-dependent Ags [7].
  • Since the antigen (Ag) specificity of CD4(+) human T cells is strongly controlled by HLA class II polymorphism, the immunogenic potential of candidate Ags needs to be defined in the context of HLA polymorphism [8].
  • These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and alpha-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies [9].
  • The results indicate that the breakpoint on the mouse X chromosome (in band XD) has separated the genes for HPRT (Hprt) and for GALA (Ags) [10].
 

Chemical compound and disease context of Gla

  • The recent generation of a matrix gamma-carboxyglutamic acid (Gla) protein (MGP) knockout mouse, which exhibits extensive and lethal calcification and cartilaginous metaplasia of the media of all elastic arteries, has refocused attention on the role of Gla-containing proteins in vascular calcification [11].
  • FcgammaR(-/-) mice, C3(-/-) mice, and immunocompetent control (B6/129Sj) mice were immunized s.c. and injected intrastromally with Onchocerca volvulus Ags [12].
  • Wild-type bone marrow rescued the humoral immune response to both Ags, i.e., the soluble Ag and HSV-1, demonstrating that local C4 production is sufficient for humoral responses [13].
  • Because IL-10-deficient mice develop colitis, and this response is triggered by luminal flora, we investigated whether IL-10 regulates the ability of microbial Ags to induce autoreactive T cells that could contribute to intestinal inflammation [14].
  • Variable Ags such as the variable major protein of Borrelia hermsii, the variant surface glycoprotein of African trypanosomes, and the pilin of Neisseria gonorrhoeae include an immunodominant variable domain and one or more invariable domains that are not antigenic [15].
 

Biological context of Gla

  • Analysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse alpha-galactosidase [16].
  • Linkage analysis involving the markers Pgk-1 and Ags indicated a gene order of centromere--Hprt--Pgk-1--Ags in crosses involving both stocks of wild mice [17].
  • We concluded that, although OC at supraphysiological levels has the potential to affect dentin mineralization probably through its Gla-residues, the locally produced levels of OC are not sufficient to markedly influence dentinogenesis [18].
  • These results demonstrate that clonal deletion is a major mechanism for tolerance to Ags previously regarded as prostate-specific, and provide direct evidence that the T cell repertoire specific for an unmutated tumor Ag can be shaped by clonal deletion in the thymus [19].
  • The conserved disulfide-bonded loop of the contryphan family of conotoxins including a D-Trp is present; however, unique to glacontryphan-M is a histidine within the intercysteine-loop and two gamma-carboxyglutamic acid (Gla) residues, formed by post-translational modification of glutamic acid [20].
 

Anatomical context of Gla

 

Associations of Gla with chemical compounds

  • In the search for a new class of bone-sparing agents for treating osteopenic disorders, we hypothesized that tartronic acid derivatives, sharing the chemical characteristics both of bisphosphonates and of Gla residues contained in matrix proteins such as osteocalcin, could positively affect bone metabolism [26].
  • Vitamin K2 is a cofactor of gamma-carboxylase, which converts the glutamic acid (Glu) residue in osteocalcin molecules to gamma-carboxyglutamic acid (Gla), and is, therefore, essential for gamma-carboxylation of osteocalcin [2].
  • The blockage of L-type voltage-gated Ca(2+) channel currents by glacontryphan-M requires calcium binding to N-terminal Gla residues, where presumably histidine and tryptophan may be accessible for interaction with the channel [20].
  • These data suggest that in addition to its recognized role in Gla synthesis, vitamin K status is important in the maintenance of normal complex lipid sulfatide metabolism in young rats and mice [27].
  • Conantokin-G (con-G) and conantokin-T (con-T) are small (17 and 21 amino acids, respectively) gamma-carboxyglutamate (Gla) containing peptides derived from the venoms of marine cone snails that are potent and selective inhibitors of N-methyl-D-aspartate (NMDA) receptors [28].
 

Physical interactions of Gla

  • The three-dimensional structure of prothrombin predicted by homology modeling also revealed that the prothrombin fragment 1 and the catalytic domain structures are well conserved except for the insertion of an extra 7-amino-acid loop in the connecting region (CR) between the Gla and kringle I domain of fragment 1 [29].
 

Enzymatic interactions of Gla

  • The liver microsomal vitamin K-dependent carboxylase catalyzes the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in precursor forms of a limited number of proteins [30].
 

Other interactions of Gla

  • The position of the amelogenin locus (Amel) relative to the loci for alpha-galactosidase (Ags), proteolipoprotein (Plp), and the random genomic probe DXWas31 has been determined [31].
  • The serum Gla-OC level in 30 healthy subjects was 3.6 +/- 2.19 ng/ml (mean +/- SD) [3].
  • These results show that different CD1.1 self Ags are expressed in different tissues and can be specifically recognized by autoreactive T cells [32].
  • We used myelin proteolipid protein (PLP) peptide 139-151 and its analogues to define motifs to search a protein database for structural homologues of PLP139-151 and identified five peptides derived from microbial Ags that elicit immune responses that cross-react with this self peptide [33].
  • The sequences of the two peptides and were determined using a combination of mass spectrometry, amino acid, and chemical sequence analyses, where Pca = pyroglutamic acid, Hyp = hydroxyproline, Gla = gamma-carboxyglutamate, and Trp* = L-6-bromotryptophan [34].
 

Analytical, diagnostic and therapeutic context of Gla

  • A highly sensitive, simple and reliable one-step sandwich enzyme immunoassay (EIA) for the gamma-carboxylated form of osteocalcin (Gla-OC) has been developed using a monoclonal antibody [3].
  • Future studies on the role of Gla-containing proteins combined with advances in noninvasive imaging techniques to quantify vascular calcification may lead to identification of individuals at particular risk of vascular calcification and the evaluation of novel therapies aimed at regulating its development or progression [11].
  • Monoclonal antibodies (McAb), isolated by affinity chromatography (Protein A-Sepharose), were tested for their affinity for normal (10-Gla) and dicoumarol-induced abnormal prothrombins containing 2, 5, 7, 8 and 9 gamma-carboxyglutamyl (Gla) residues [35].
  • Additionally, 2 to 4 months after transplantation, T cells from these mice were tolerant to host non H-2 antigens but kept reactivity against third-party Ags [36].
  • Therefore, CpG adjuvant-guided induction of type 1 immunity against tumor Ags might be a promising subunit vaccination approach [37].

References

  1. Fabry disease in mice is associated with age-dependent susceptibility to vascular thrombosis. Eitzman, D.T., Bodary, P.F., Shen, Y., Khairallah, C.G., Wild, S.R., Abe, A., Shaffer-Hartman, J., Shayman, J.A. J. Am. Soc. Nephrol. (2003) [Pubmed]
  2. Effects of vitamin K2 on osteoporosis. Iwamoto, J., Takeda, T., Sato, Y. Curr. Pharm. Des. (2004) [Pubmed]
  3. A one step sandwich enzyme immunoassay for gamma-carboxylated osteocalcin using monoclonal antibodies. Koyama, N., Ohara, K., Yokota, H., Kurome, T., Katayama, M., Hino, F., Kato, I., Akai, T. J. Immunol. Methods (1991) [Pubmed]
  4. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse T cell repertoire. Kuchroo, V.K., Greer, J.M., Kaul, D., Ishioka, G., Franco, A., Sette, A., Sobel, R.A., Lees, M.B. J. Immunol. (1994) [Pubmed]
  5. A novel Plasmodium falciparum sporozoite and liver stage antigen (SALSA) defines major B, T helper, and CTL epitopes. Bottius, E., BenMohamed, L., Brahimi, K., Gras, H., Lepers, J.P., Raharimalala, L., Aikawa, M., Meis, J., Slierendregt, B., Tartar, A., Thomas, A., Druilhe, P. J. Immunol. (1996) [Pubmed]
  6. Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Munroe, P.B., Olgunturk, R.O., Fryns, J.P., Van Maldergem, L., Ziereisen, F., Yuksel, B., Gardiner, R.M., Chung, E. Nat. Genet. (1999) [Pubmed]
  7. Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses. Kuwahara, K., Fujimura, S., Takahashi, Y., Nakagata, N., Takemori, T., Aizawa, S., Sakaguchi, N. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Identification of HLA class II-restricted determinants of Mycobacterium tuberculosis-derived proteins by using HLA-transgenic, class II-deficient mice. Geluk, A., Taneja, V., van Meijgaarden, K.E., Zanelli, E., Abou-Zeid, C., Thole, J.E., de Vries, R.R., David, C.S., Ottenhoff, T.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome. Avner, P., Arnaud, D., Amar, L., Cambrou, J., Winking, H., Russell, L.B. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  10. Comparative gene mapping: order of loci on the X chromosome is different in mice and humans. Francke, U., Taggart, R.T. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  11. The role of Gla proteins in vascular calcification. Shanahan, C.M., Proudfoot, D., Farzaneh-Far, A., Weissberg, P.L. Crit. Rev. Eukaryot. Gene Expr. (1998) [Pubmed]
  12. A dominant role for Fc gamma receptors in antibody-dependent corneal inflammation. Hall, L.R., Diaconu, E., Pearlman, E. J. Immunol. (2001) [Pubmed]
  13. Macrophage-derived complement component C4 can restore humoral immunity in C4-deficient mice. Gadjeva, M., Verschoor, A., Brockman, M.A., Jezak, H., Shen, L.M., Knipe, D.M., Carroll, M.C. J. Immunol. (2002) [Pubmed]
  14. Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: regulation of autoreactive responses by IL-10. Ito, K., Takaishi, H., Jin, Y., Song, F., Denning, T.L., Ernst, P.B. J. Immunol. (2000) [Pubmed]
  15. An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. Liang, F.T., Alvarez, A.L., Gu, Y., Nowling, J.M., Ramamoorthy, R., Philipp, M.T. J. Immunol. (1999) [Pubmed]
  16. X-linked and autosomal genes controlling mouse alpha-galactosidase expression. Lusis, A.J., West, J.D. Genetics (1978) [Pubmed]
  17. Electrophoretic variation for X chromosome-linked hypoxanthine phosphoribosyl transferase (HPRT) in wild-derived mice. Chapman, V.M., Kratzer, P.G., Quarantillo, B.A. Genetics (1983) [Pubmed]
  18. Studies of osteocalcin function in dentin formation in rodent teeth. Bronckers, A.L., Price, P.A., Schrijvers, A., Bervoets, T.J., Karsenty, G. Eur. J. Oral Sci. (1998) [Pubmed]
  19. Clonal deletion of simian virus 40 large T antigen-specific T cells in the transgenic adenocarcinoma of mouse prostate mice: an important role for clonal deletion in shaping the repertoire of T cells specific for antigens overexpressed in solid tumors. Zheng, X., Gao, J.X., Zhang, H., Geiger, T.L., Liu, Y., Zheng, P. J. Immunol. (2002) [Pubmed]
  20. The metal-free and calcium-bound structures of a gamma-carboxyglutamic acid-containing contryphan from Conus marmoreus, glacontryphan-M. Grant, M.A., Hansson, K., Furie, B.C., Furie, B., Stenflo, J., Rigby, A.C. J. Biol. Chem. (2004) [Pubmed]
  21. Tolerant CD8 T cells induced by multiple injections of peptide antigen show impaired TCR signaling and altered proliferative responses in vitro and in vivo. Dubois, P.M., Pihlgren, M., Tomkowiak, M., Van Mechelen, M., Marvel, J. J. Immunol. (1998) [Pubmed]
  22. A structurally available encephalitogenic epitope of myelin oligodendrocyte glycoprotein specifically induces a diversified pathogenic autoimmune response. Bischof, F., Bins, A., Dürr, M., Zevering, Y., Melms, A., Kruisbeek, A.M. J. Immunol. (2004) [Pubmed]
  23. Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and B10.S mice. Encinas, J.A., Lees, M.B., Sobel, R.A., Symonowicz, C., Greer, J.M., Shovlin, C.L., Weiner, H.L., Seidman, C.E., Seidman, J.G., Kuchroo, V.K. J. Immunol. (1996) [Pubmed]
  24. Vascular smooth muscle cell-derived, Gla-containing growth-potentiating factor for Ca(2+)-mobilizing growth factors. Nakano, T., Higashino, K., Kikuchi, N., Kishino, J., Nomura, K., Fujita, H., Ohara, O., Arita, H. J. Biol. Chem. (1995) [Pubmed]
  25. Crystallization of an anti-factor IX antibody and its complex. Shi, X., Li, Y., Bian, C., Zhao, G., Huang, M. Acta Crystallogr. D Biol. Crystallogr. (2005) [Pubmed]
  26. Tartronates: a new generation of drugs affecting bone metabolism. Caselli, G., Mantovanini, M., Gandolfi, C.A., Allegretti, M., Fiorentino, S., Pellegrini, L., Melillo, G., Bertini, R., Sabbatini, W., Anacardio, R., Clavenna, G., Sciortino, G., Teti, A. J. Bone Miner. Res. (1997) [Pubmed]
  27. Vitamin K status influences brain sulfatide metabolism in young mice and rats. Sundaram, K.S., Fan, J.H., Engelke, J.A., Foley, A.L., Suttie, J.W., Lev, M. J. Nutr. (1996) [Pubmed]
  28. Inhibition of NMDA-induced currents by conantokin-G and conantokin-T in cultured embryonic murine hippocampal neurons. Klein, R.C., Galdzicki, Z., Castellino, F.J. Neuropharmacology (1999) [Pubmed]
  29. Characterization of zebrafish full-length prothrombin cDNA and linkage group mapping. Jagadeeswaran, P., Gregory, M., Zhou, Y., Zon, L., Padmanabhan, K., Hanumanthaiah, R. Blood Cells Mol. Dis. (2000) [Pubmed]
  30. Vitamin K-dependent carboxylase: influence of the "propeptide" region on enzyme activity. Cheung, A., Engelke, J.A., Sanders, C., Suttie, J.W. Arch. Biochem. Biophys. (1989) [Pubmed]
  31. Linkage of amelogenin (Amel) to the distal portion of the mouse X chromosome. Chapman, V.M., Keitz, B.T., Disteche, C.M., Lau, E.C., Snead, M.L. Genomics (1991) [Pubmed]
  32. Tissue-specific recognition of mouse CD1 molecules. Park, S.H., Roark, J.H., Bendelac, A. J. Immunol. (1998) [Pubmed]
  33. Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen. Carrizosa, A.M., Nicholson, L.B., Farzan, M., Southwood, S., Sette, A., Sobel, R.A., Kuchroo, V.K. J. Immunol. (1998) [Pubmed]
  34. A novel post-translational modification involving bromination of tryptophan. Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom. Craig, A.G., Jimenez, E.C., Dykert, J., Nielsen, D.B., Gulyas, J., Abogadie, F.C., Porter, J., Rivier, J.E., Cruz, L.J., Olivera, B.M., McIntosh, J.M. J. Biol. Chem. (1997) [Pubmed]
  35. Monoclonal antibodies to prothrombin. Malhotra, O.P., Sudilovsky, O. Thromb. Res. (1987) [Pubmed]
  36. Newborn blood can engraft adult mice without inducing graft-versus-host disease across non H-2 antigens. de La Selle, V., Gluckman, E., Bruley-Rosset, M. Blood (1996) [Pubmed]
  37. Vaccination with tumor peptide in CpG adjuvant protects via IFN-gamma-dependent CD4 cell immunity. Stern, B.V., Boehm, B.O., Tary-Lehmann, M. J. Immunol. (2002) [Pubmed]
 
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