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GLB1

{{Short description|Protein}}

{{Infobox_gene}}

Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene.{{cite journal | vauthors = Shows TB, Scrafford-Wolff L, Brown JA, Meisler M | title = Assignment of a beta-galactosidase gene (beta GALA) to chromosome 3 in man | journal = Cytogenetics and Cell Genetics | volume = 22 | issue = 1–6 | pages = 219–22 | year = 1978 | pmid = 110522 | doi = 10.1159/000130940 }}{{cite journal | vauthors = Oshima A, Tsuji A, Nagao Y, Sakuraba H, Suzuki Y | title = Cloning, sequencing, and expression of cDNA for human beta-galactosidase | journal = Biochemical and Biophysical Research Communications | volume = 157 | issue = 1 | pages = 238–44 | date = Nov 1988 | pmid = 3143362 | doi = 10.1016/S0006-291X(88)80038-X }}

The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates.{{cite journal | vauthors = Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y | title = Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases | journal = American Journal of Human Genetics | volume = 49 | issue = 2 | pages = 435–42 | date = Aug 1991 | pmid = 1907800 | pmc = 1683306 }} The GLB1 gene also encodes an elastin binding protein.{{cite journal | vauthors = Caciotti A, Donati MA, Boneh A, d'Azzo A, Federico A, Parini R, Antuzzi D, Bardelli T, Nosi D, Kimonis V, Zammarchi E, Morrone A | title = Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis | journal = Human Mutation | volume = 25 | issue = 3 | pages = 285–92 | date = Mar 2005 | pmid = 15714521 | doi = 10.1002/humu.20147 | s2cid = 36584440 | hdl = 2158/312510 | hdl-access = free }}

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.{{cite journal | vauthors = Hinek A, Zhang S, Smith AC, Callahan JW | title = 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 | journal = American Journal of Human Genetics | volume = 67 | issue = 1 | pages = 23–36 | date = Jul 2000 | pmid = 10841810 | pmc = 1287082 | doi = 10.1086/302968 | url = http://www.jbc.org/cgi/content/full/273/11/6319 | access-date = 2009-05-31 | archive-date = 2005-01-18 | archive-url = https://web.archive.org/web/20050118201219/http://www.jbc.org/cgi/content/full/273/11/6319 | url-status = dead }}

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.{{cite journal | vauthors = Privitera S, Prody CA, Callahan JW, Hinek A | title = The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein | journal = The Journal of Biological Chemistry | volume = 273 | issue = 11 | pages = 6319–26 | date = Mar 1998 | pmid = 9497360 | doi = 10.1074/jbc.273.11.6319 | url = http://www.jbc.org/cgi/content/full/273/11/6319 | doi-access = free | access-date = 2009-05-31 | archive-date = 2005-01-18 | archive-url = https://web.archive.org/web/20050118201219/http://www.jbc.org/cgi/content/full/273/11/6319 | url-status = dead }}

The S-Gal protein is a peripheral membrane protein that functions as part of an elastin receptor complex on the surface of cells.{{cite journal | vauthors = Duca L, Blanchevoye C, Cantarelli B, Ghoneim C, Dedieu S, Delacoux F, Hornebeck W, Hinek A, Martiny L, Debelle L | title = The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit | journal = The Journal of Biological Chemistry | volume = 282 | issue = 17 | pages = 12484–91 | date = Apr 2007 | pmid = 17327233 | doi = 10.1074/jbc.M609505200 | url = http://www.jbc.org/cgi/content/full/282/17/12484 | doi-access = free | access-date = 2009-05-31 | archive-date = 2008-09-22 | archive-url = https://web.archive.org/web/20080922051001/http://www.jbc.org/cgi/content/full/282/17/12484 | url-status = dead }} 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{{cite journal | vauthors = Adair-Kirk TL, Senior RM | title = Fragments of extracellular matrix as mediators of inflammation | journal = The International Journal of Biochemistry & Cell Biology | volume = 40 | issue = 6–7 | pages = 1101–10 | date = December 2008 | pmid = 18243041 | pmc = 2478752 | doi = 10.1016/j.biocel.2007.12.005 }} and can alter cell cycle progression.{{cite journal | vauthors = Hinek A, Bodnaruk TD, Bunda S, Wang Y, Liu K | title = 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 | journal = The American Journal of Pathology | volume = 173 | issue = 4 | pages = 1042–56 | date = Oct 2008 | pmid = 18772331 | pmc = 2543072 | doi = 10.2353/ajpath.2008.071081 }} 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.{{cite journal | vauthors = Hinek A, Pshezhetsky AV, von Itzstein M, Starcher B | title = Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly | journal = The Journal of Biological Chemistry | volume = 281 | issue = 6 | pages = 3698–710 | date = Feb 2006 | pmid = 16314420 | doi = 10.1074/jbc.M508736200 | url = http://www.jbc.org/cgi/content/full/281/6/3698 | doi-access = free | access-date = 2009-05-31 | archive-date = 2008-09-19 | archive-url = https://web.archive.org/web/20080919153253/http://www.jbc.org/cgi/content/full/281/6/3698 | url-status = dead }} Cathepsin A is also required for normal elastin biosynthesis.{{cite journal | vauthors = Seyrantepe V, Hinek A, Peng J, Fedjaev M, Ernest S, Kadota Y, Canuel M, Itoh K, Morales CR, Lavoie J, Tremblay J, Pshezhetsky AV | title = Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1 | journal = Circulation | volume = 117 | issue = 15 | pages = 1973–81 | date = Apr 2008 | pmid = 18391110 | doi = 10.1161/CIRCULATIONAHA.107.733212 | url = http://www.jbc.org/cgi/content/full/281/6/3698 | doi-access = free | access-date = 2009-05-31 | archive-date = 2008-09-19 | archive-url = https://web.archive.org/web/20080919153253/http://www.jbc.org/cgi/content/full/281/6/3698 | url-status = dead }}

References

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Further reading

{{refbegin|33em}}

  • {{cite journal | vauthors = Hinek A | title = Biological roles of the non-integrin elastin/laminin receptor | journal = Biological Chemistry | volume = 377 | issue = 7–8 | pages = 471–80 | year = 1997 | pmid = 8922281 | doi = 10.1515/bchm3.1996.377.7-8.411 }}
  • {{cite journal | vauthors = Kaye EM, Shalish C, Livermore J, Taylor HA, Stevenson RE, Breakefield XO | title = beta-Galactosidase gene mutations in patients with slowly progressive GM1 gangliosidosis | journal = Journal of Child Neurology | volume = 12 | issue = 4 | pages = 242–7 | date = Jun 1997 | pmid = 9203065 | doi = 10.1177/088307389701200404 | s2cid = 27281171 }}
  • {{cite journal | vauthors = Callahan JW | title = 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 | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1455 | issue = 2–3 | pages = 85–103 | date = Oct 1999 | pmid = 10571006 | doi = 10.1016/S0925-4439(99)00075-7 | doi-access = free }}
  • {{cite journal | vauthors = Shows TB, Scrafford-Wolff L, Brown JA, Meisler M | title = Assignment of a beta-galactosidase gene (beta GALA) to chromosome 3 in man | journal = Cytogenetics and Cell Genetics | volume = 22 | issue = 1–6 | pages = 219–22 | year = 1979 | pmid = 110522 | doi = 10.1159/000130940 }}
  • {{cite journal | vauthors = Shows TB, Scrafford-Wolff LR, Brown JA, Meisler MH | title = GM1-gangliosidosis: chromosome 3 assignment of the beta-galactosidase-A gene (beta GALA) | journal = Somatic Cell Genetics | volume = 5 | issue = 2 | pages = 147–58 | date = Mar 1979 | pmid = 113895 | doi = 10.1007/BF01539157 | hdl = 2027.42/45554 | s2cid = 21896411 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/45554/1/11188_2005_Article_BF01539157.pdf | hdl-access = free }}
  • {{cite journal | vauthors = Yoshida K, Oshima A, Sakuraba H, Nakano T, Yanagisawa N, Inui K, Okada S, Uyama E, Namba R, Kondo K | title = GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients | journal = Annals of Neurology | volume = 31 | issue = 3 | pages = 328–32 | date = Mar 1992 | pmid = 1353343 | doi = 10.1002/ana.410310316 | s2cid = 5103186 }}
  • {{cite journal | vauthors = Mosna G, Fattore S, Tubiello G, Brocca S, Trubia M, Gianazza E, Gatti R, Danesino C, Minelli A, Piantanida M | title = A homozygous missense arginine to histidine substitution at position 482 of the beta-galactosidase in an Italian infantile GM1-gangliosidosis patient | journal = Human Genetics | volume = 90 | issue = 3 | pages = 247–50 | date = Nov 1992 | pmid = 1487238 | doi = 10.1007/bf00220071 | s2cid = 21873727 }}
  • {{cite journal | vauthors = Oshima A, Yoshida K, Ishizaki A, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y | title = GM1-gangliosidosis: tandem duplication within exon 3 of beta-galactosidase gene in an infantile patient | journal = Clinical Genetics | volume = 41 | issue = 5 | pages = 235–8 | date = May 1992 | pmid = 1606711 | doi = 10.1111/j.1399-0004.1992.tb03672.x | s2cid = 21921420 }}
  • {{cite journal | vauthors = Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y | title = Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases | journal = American Journal of Human Genetics | volume = 49 | issue = 2 | pages = 435–42 | date = Aug 1991 | pmid = 1907800 | pmc = 1683306 }}
  • {{cite journal | vauthors = Nishimoto J, Nanba E, Inui K, Okada S, Suzuki K | title = GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients | journal = American Journal of Human Genetics | volume = 49 | issue = 3 | pages = 566–74 | date = Sep 1991 | pmid = 1909089 | pmc = 1683129 }}
  • {{cite journal | vauthors = Morreau H, Bonten E, Zhou XY, D'Azzo A | title = Organization of the gene encoding human lysosomal beta-galactosidase | journal = DNA and Cell Biology | volume = 10 | issue = 7 | pages = 495–504 | date = Sep 1991 | pmid = 1909871 | doi = 10.1089/dna.1991.10.495 }}
  • {{cite journal | vauthors = Oshima A, Yoshida K, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y | title = Human beta-galactosidase gene mutations in morquio B disease | journal = American Journal of Human Genetics | volume = 49 | issue = 5 | pages = 1091–3 | date = Nov 1991 | pmid = 1928092 | pmc = 1683264 }}
  • {{cite journal | vauthors = Yamamoto Y, Hake CA, Martin BM, Kretz KA, Ahern-Rindell AJ, Naylor SL, Mudd M, O'Brien JS | title = Isolation, characterization, and mapping of a human acid beta-galactosidase cDNA | journal = DNA and Cell Biology | volume = 9 | issue = 2 | pages = 119–27 | date = Mar 1990 | pmid = 2111707 | doi = 10.1089/dna.1990.9.119 }}
  • {{cite journal | vauthors = Morreau H, Galjart NJ, Gillemans N, Willemsen R, van der Horst GT, d'Azzo A | title = Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein | journal = The Journal of Biological Chemistry | volume = 264 | issue = 34 | pages = 20655–63 | date = Dec 1989 | doi = 10.1016/S0021-9258(19)47114-7 | pmid = 2511208 | doi-access = free }}
  • {{cite journal | vauthors = Hoogeveen AT, Reuser AJ, Kroos M, Galjaard H | title = GM1-gangliosidosis. Defective recognition site on beta-galactosidase precursor | journal = The Journal of Biological Chemistry | volume = 261 | issue = 13 | pages = 5702–4 | date = May 1986 | doi = 10.1016/S0021-9258(17)38439-9 | pmid = 3084469 | doi-access = free }}
  • {{cite journal | vauthors = Verheijen FW, Palmeri S, Galjaard H | title = Purification and partial characterization of lysosomal neuraminidase from human placenta | journal = European Journal of Biochemistry | volume = 162 | issue = 1 | pages = 63–7 | date = Jan 1987 | pmid = 3102233 | doi = 10.1111/j.1432-1033.1987.tb10542.x | doi-access = free }}
  • {{cite journal | vauthors = Oshima A, Tsuji A, Nagao Y, Sakuraba H, Suzuki Y | title = Cloning, sequencing, and expression of cDNA for human beta-galactosidase | journal = Biochemical and Biophysical Research Communications | volume = 157 | issue = 1 | pages = 238–44 | date = Nov 1988 | pmid = 3143362 | doi = 10.1016/S0006-291X(88)80038-X }}
  • {{cite journal | vauthors = Sips HJ, de Wit-Verbeek HA, de Wit J, Westerveld A, Galjaard H | title = 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 | journal = Human Genetics | volume = 69 | issue = 4 | pages = 340–4 | year = 1985 | pmid = 3921454 | doi = 10.1007/BF00291653 | s2cid = 26594537 }}
  • {{cite journal | vauthors = Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H | title = Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein | journal = European Journal of Biochemistry | volume = 149 | issue = 2 | pages = 315–21 | date = Jun 1985 | pmid = 3922758 | doi = 10.1111/j.1432-1033.1985.tb08928.x | doi-access = free }}
  • {{cite journal | vauthors = Goldman JE, Katz D, Rapin I, Purpura DP, Suzuki K | title = Chronic GM1 gangliosidosis presenting as dystonia: I. Clinical and pathological features | journal = Annals of Neurology | volume = 9 | issue = 5 | pages = 465–75 | date = May 1981 | pmid = 6791574 | doi = 10.1002/ana.410090509 | s2cid = 26073976 }}

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{{Proteoglycan metabolism enzymes}}