Alternative titles; symbols
HGNC Approved Gene Symbol: FUCA2
Cytogenetic location: 6q24.2 Genomic coordinates (GRCh38): 6:143,494,812-143,511,720 (from NCBI)
Fucosylated proteins are involved in a variety of processes, including immune response, signal transduction, embryogenesis and development, apoptosis, adhesion, and extravasation of leukocytes. Alpha-L-fucosidases (EC 3.2.1.51), such as FUCA2, are exoglycosidases that catalyze the removal of terminal L-fucose residues linked via alpha-1,2, alpha-1,3, alpha-1,4, or alpha-1,6 to the reducing end of N-acetyl glucosamine of oligosaccharide chains. Alpha-L-fucosidases may also have transglycosylation properties (summary by Intra et al., 2007).
By database analysis, Intra et al. (2007) identified orthologs of FUCA2 in a variety of organisms, including bacteria, fungi, invertebrates, birds, and mammals. The deduced 467-amino acid human FUCA2 protein contains an N-terminal signal sequence followed by a catalytic domain. FUCA2 may also have 2 transmembrane helices that are not well conserved.
By coculturing Helicobacter pylori (see 600263) with gastric cancer (613659) cells, Liu et al. (2009) found that FUCA2 was secreted by infected cells and was key to the transfer of L-fucose from the surface of gastric cancer cells to clinical strains of H. pylori. Depletion of FUCA2 by RNA interference showed that the enzyme was essential for H. pylori adhesion to gastric cancer cells, particularly by gastric cancer- and duodenal ulcer-specific strains. FUCA2 also enhanced expression of Lewis x antigen (see 602030) in H. pylori. Liu et al. (2009) concluded that there is an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori and suggested that FUCA2 is a potential target for clinical diagnosis and therapy of H. pylori-related diseases.
Intra et al. (2007) determined that the FUCA2 gene contains 7 exons and spans 16.9 kb.
Alpha-L-fucosidase-2 is coded by a gene linked to plasminogen (PLG; 173350). Eiberg and Mohr (1984) found, for the PLG:FUCA2 linkage, a lod score of 7.37 at theta = 0.10 for males and 4.64 at 0.19 for females. Eiberg et al. (1984) found a lod score of 7.37 at theta = 0.12 in males for linkage of FUCA2 and PLG. Linkage of PLG with GC (and therefore location on chromosome 4) was suggested by a lod score of 2.35 at theta = 0.30 in males. However, once the plasminogen locus was found to be on chromosome 6, FUCA2 could be assigned to chromosome 6 also.
Hartz (2011) mapped the FUCA2 gene to chromosome 6q24.2 based on an alignment of the FUCA2 sequence (GenBank AK075458) with the genomic sequence (GRCh37).
The FUCA2 locus regulates the level of alpha-fucosidase in plasma (Ng et al., 1976) and fibroblasts (Van Elsen et al., 1983), but not in leukocytes. Wood (1979) suggested that the frequency of low plasma fucosidase (62%) makes it a useful marker in linkage studies. Wood (1977) argued that plasma and leukocyte alpha-L-fucosidases are under the same genetic control and that the electrophoretic polymorphism of the enzyme in leukocytes and the enzyme in fucosidosis is determined by mutations at the same locus. In fucosidosis, deficiency of alpha-L-fucosidase is found in both plasma and leukocytes. Normal individuals with low plasma enzyme but normal leukocyte enzyme were described by Ng et al. (1976); however, plasma enzyme is different electrophoretically from leukocyte enzyme. The level of plasma fucosidase could be explained on the basis of 2 alleles leading to three phenotypes of high, intermediate, and low enzyme levels.
Low activity of alpha-L-fucosidase in the plasma is found in about 10% of persons (Ng et al., 1976; Playfer and Evans, 1976; Gatti et al., 1979) and is genetically determined. The frequency distribution of plasma fucosidase activity in the population shows bimodality with 1 group consisting of persons with low activity thought to be due to homozygosity for a recessive gene and a second larger group consisting of heterozygotes and normal homozygotes. Complex segregation analysis supported this interpretation (Iselius et al., 1982). Van Elsen et al. (1983) showed that this polymorphism is not limited to plasma but is found also in cultured fibroblasts.
Eiberg, H., Mohr, J. Synteny of plasma alpha-L-fucosidase (FUCA2) and the plasminogen (PLG) system. (Abstract) Cytogenet. Cell Genet. 37: 460 only, 1984.
Eiberg, H., Mohr, J., Nielsen, L. S. Linkage of plasma alpha-L-fucosidase (FUCA2) and the plasminogen (PLG) system. Clin. Genet. 26: 23-29, 1984. [PubMed: 6590153] [Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00782.x]
Gatti, R., Cavalieri, S., Romeo, G. Relationship between alpha-L-fucosidase deficiency in plasma and alpha-L-fucosidase activity in leucocytes. Hum. Genet. 48: 23-30, 1979. [PubMed: 457132] [Full Text: https://doi.org/10.1007/BF00273270]
Hartz, P. A. Personal Communication. Baltimore, Md. 11/8/2011.
Intra, J., Perotti, M.-E., Pavesi, G., Horner, D. Comparative and phylogenetic analysis of alpha-L-fucosidase genes. Gene 392: 34-46, 2007. [PubMed: 17175120] [Full Text: https://doi.org/10.1016/j.gene.2006.11.002]
Iselius, L., Playfer, J. R., Evans, D. A. P. Segregation analysis of alpha-L-fucosidase activity. Hum. Genet. 60: 271-273, 1982. [PubMed: 7106758] [Full Text: https://doi.org/10.1007/BF00303016]
Liu, T.-W., Ho, C.-W., Huang, H.-H., Chang, S.-M., Popat, S. D., Wang, Y.-T., Wu, M.-S., Chen, Y.-J., Lin, C.-H. Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells. Proc. Nat. Acad. Sci. 106: 14581-14586, 2009. [PubMed: 19666478] [Full Text: https://doi.org/10.1073/pnas.0903286106]
Ng, W. G., Donnell, G. N., Koch, R., Bergren, W. R. Biochemical and genetic studies of plasma and leukocyte alpha-L-fucosidase. Am. J. Hum. Genet. 28: 42-50, 1976. [PubMed: 1247019]
Playfer, J. R., Evans, D. A. P. Enzyme activity in fucosidosis. Lancet 308: 1415-1416, 1976. Note: Originally Volume II. [PubMed: 63883] [Full Text: https://doi.org/10.1016/s0140-6736(76)91961-9]
Van Elsen, A. F., Leroy, J. G., Wauters, J. G., Willems, P. J., Buytaert, C., Verheyen, K. In vitro expression of alpha-L-fucosidase activity polymorphism observed in plasma. Hum. Genet. 64: 235-239, 1983. [PubMed: 6885067] [Full Text: https://doi.org/10.1007/BF00279400]
Wood, S. Human alpha-L-fucosidase: a common polymorphic variant for low serum enzyme activity: studies of serum and leukocyte enzyme. Hum. Hered. 29: 226-229, 1979. [PubMed: 478557] [Full Text: https://doi.org/10.1159/000153049]
Wood, S. Genetic control of alpha-L-fucosidase. (Letter) Lancet 309: 368 only, 1977. Note: Originally Volume I. [PubMed: 64893] [Full Text: https://doi.org/10.1016/s0140-6736(77)91174-6]