Biology:GLB1
 Generic protein structure example |
Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene.[1][2]
The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates.[3] The GLB1 gene also encodes an elastin binding protein.[4]
In corn (Zea mays), Glb1 is a gene coding for the storage protein globulin.
Clinical significance
GM1-gangliosidosis is a lysosomal storage disease that can be caused by a deficiency of β-galactosidase (GLB1). Some cases of Morquio syndrome B have been shown to be due to GLP1 mutations that cause patients to have abnormal elastic fibers.[5]
Elastin receptor
The RNA transcript of the GLB1 gene is alternatively spliced and produces 2 mRNAs. The 2.5-kilobase transcript encodes the beta-galactosidase enzyme of 677 amino acids. The alternative 2.0-kb mRNA encodes a beta-galactosidase-related protein (S-Gal) that is only 546 amino acids long and that has no enzymatic activity. The S-Gal protein does bind elastin and fragments of elastin that are generated by proteolysis.[6]
The S-Gal protein is a peripheral membrane protein that functions as part of an elastin receptor complex on the surface of cells.[7] The elastin receptor complex includes S-Gal, neuraminidase and Cathepsin A. When elastin-derived peptides bind to the S-Gal protein then the associated neuraminidase enzyme activity is activated and responding cells can have altered signal transduction involving extracellular signal-regulated kinases and regulated matrix metallopeptidase production. Elastin-derived peptides are chemotactic for some cell types[8] and can alter cell cycle progression.[9] The ability of the GLB1-derived elastin binding protein and the elastin receptor complex to influence cell proliferation appears to be indirect and involve removal of sialic acid from extracellular and cell surface proteins such as growth factor receptors.
The S-Gal protein functions during the normal assembly of elastin into extracellular elastic fibers. Elastin is initially present as newly synthesized tropoelastin which can be found in association with S-Gal. The enzymatic activity of neuraminidase in the elastin receptor complex is involved in the release of tropoelastin molecules from the S-Gal chaperone.[10] Cathepsin A is also required for normal elastin biosynthesis.[11]
References
- ↑ "Assignment of a beta-galactosidase gene (beta GALA) to chromosome 3 in man". Cytogenetics and Cell Genetics 22 (1–6): 219–22. 1978. doi:10.1159/000130940. PMID 110522.
- ↑ "Cloning, sequencing, and expression of cDNA for human beta-galactosidase". Biochemical and Biophysical Research Communications 157 (1): 238–44. Nov 1988. doi:10.1016/S0006-291X(88)80038-X. PMID 3143362.
- ↑ "Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases". American Journal of Human Genetics 49 (2): 435–42. Aug 1991. PMID 1907800.
- ↑ "Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis". Human Mutation 25 (3): 285–92. Mar 2005. doi:10.1002/humu.20147. PMID 15714521.
- ↑ "Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase". American Journal of Human Genetics 67 (1): 23–36. Jul 2000. doi:10.1086/302968. PMID 10841810. PMC 1287082. http://www.jbc.org/cgi/content/full/273/11/6319.
- ↑ "The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein". The Journal of Biological Chemistry 273 (11): 6319–26. Mar 1998. doi:10.1074/jbc.273.11.6319. PMID 9497360. http://www.jbc.org/cgi/content/full/273/11/6319.
- ↑ "The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit". The Journal of Biological Chemistry 282 (17): 12484–91. Apr 2007. doi:10.1074/jbc.M609505200. PMID 17327233. http://www.jbc.org/cgi/content/full/282/17/12484.
- ↑ "Fragments of extracellular matrix as mediators of inflammation". The International Journal of Biochemistry & Cell Biology 40 (6–7): 1101–10. December 2008. doi:10.1016/j.biocel.2007.12.005. PMID 18243041.
- ↑ "Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors PDGF-BB and IGF-2". The American Journal of Pathology 173 (4): 1042–56. Oct 2008. doi:10.2353/ajpath.2008.071081. PMID 18772331.
- ↑ "Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly". The Journal of Biological Chemistry 281 (6): 3698–710. Feb 2006. doi:10.1074/jbc.M508736200. PMID 16314420. http://www.jbc.org/cgi/content/full/281/6/3698.
- ↑ "Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1". Circulation 117 (15): 1973–81. Apr 2008. doi:10.1161/CIRCULATIONAHA.107.733212. PMID 18391110. http://www.jbc.org/cgi/content/full/281/6/3698.
Further reading
- "Biological roles of the non-integrin elastin/laminin receptor". Biological Chemistry 377 (7–8): 471–80. 1997. doi:10.1515/bchm3.1996.377.7-8.411. PMID 8922281.
- "beta-Galactosidase gene mutations in patients with slowly progressive GM1 gangliosidosis". Journal of Child Neurology 12 (4): 242–7. Jun 1997. doi:10.1177/088307389701200404. PMID 9203065.
- "Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1455 (2–3): 85–103. Oct 1999. doi:10.1016/S0925-4439(99)00075-7. PMID 10571006.
- "Assignment of a beta-galactosidase gene (beta GALA) to chromosome 3 in man". Cytogenetics and Cell Genetics 22 (1–6): 219–22. 1979. doi:10.1159/000130940. PMID 110522.
- "GM1-gangliosidosis: chromosome 3 assignment of the beta-galactosidase-A gene (beta GALA)". Somatic Cell Genetics 5 (2): 147–58. Mar 1979. doi:10.1007/BF01539157. PMID 113895. https://deepblue.lib.umich.edu/bitstream/2027.42/45554/1/11188_2005_Article_BF01539157.pdf.
- "GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients". Annals of Neurology 31 (3): 328–32. Mar 1992. doi:10.1002/ana.410310316. PMID 1353343.
- "A homozygous missense arginine to histidine substitution at position 482 of the beta-galactosidase in an Italian infantile GM1-gangliosidosis patient". Human Genetics 90 (3): 247–50. Nov 1992. doi:10.1007/bf00220071. PMID 1487238.
- "GM1-gangliosidosis: tandem duplication within exon 3 of beta-galactosidase gene in an infantile patient". Clinical Genetics 41 (5): 235–8. May 1992. doi:10.1111/j.1399-0004.1992.tb03672.x. PMID 1606711.
- "Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases". American Journal of Human Genetics 49 (2): 435–42. Aug 1991. PMID 1907800.
- "GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients". American Journal of Human Genetics 49 (3): 566–74. Sep 1991. PMID 1909089.
- "Organization of the gene encoding human lysosomal beta-galactosidase". DNA and Cell Biology 10 (7): 495–504. Sep 1991. doi:10.1089/dna.1991.10.495. PMID 1909871.
- "Human beta-galactosidase gene mutations in morquio B disease". American Journal of Human Genetics 49 (5): 1091–3. Nov 1991. PMID 1928092.
- "Isolation, characterization, and mapping of a human acid beta-galactosidase cDNA". DNA and Cell Biology 9 (2): 119–27. Mar 1990. doi:10.1089/dna.1990.9.119. PMID 2111707.
- "Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein". The Journal of Biological Chemistry 264 (34): 20655–63. Dec 1989. doi:10.1016/S0021-9258(19)47114-7. PMID 2511208.
- "GM1-gangliosidosis. Defective recognition site on beta-galactosidase precursor". The Journal of Biological Chemistry 261 (13): 5702–4. May 1986. doi:10.1016/S0021-9258(17)38439-9. PMID 3084469.
- "Purification and partial characterization of lysosomal neuraminidase from human placenta". European Journal of Biochemistry 162 (1): 63–7. Jan 1987. doi:10.1111/j.1432-1033.1987.tb10542.x. PMID 3102233.
- "Cloning, sequencing, and expression of cDNA for human beta-galactosidase". Biochemical and Biophysical Research Communications 157 (1): 238–44. Nov 1988. doi:10.1016/S0006-291X(88)80038-X. PMID 3143362.
- "The chromosomal localization of human beta-galactosidase revisited: a locus for beta-galactosidase on human chromosome 3 and for its protective protein on human chromosome 22". Human Genetics 69 (4): 340–4. 1985. doi:10.1007/BF00291653. PMID 3921454.
- "Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein". European Journal of Biochemistry 149 (2): 315–21. Jun 1985. doi:10.1111/j.1432-1033.1985.tb08928.x. PMID 3922758.
- "Chronic GM1 gangliosidosis presenting as dystonia: I. Clinical and pathological features". Annals of Neurology 9 (5): 465–75. May 1981. doi:10.1002/ana.410090509. PMID 6791574.
 |  |
